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S1083879119305592 | Mycosis fungoides and Szary syndrome are the most common types of primary cutaneous T cell lymphomas . The clinical presentation of mycosis fungoides is generally indolent whereas Szary syndrome represents a more aggressive disease variant . Stage at diagnosis is the most important determinant of long term survival outcome . Although most patients present with early stage disease those who develop progressive disease or have an advanced stage represent a therapeutic challenge because of a lack of effective therapies . Allogeneic hematopoietic cell transplantation has been used as a potentially curative treatment modality with encouraging long term outcomes . However a lack of randomized controlled data remains and the published literature is limited to mostly retrospective studies . We performed a comprehensive search of the medical literature using PubMed Medline EMBASE and Cochrane reviews on September 13 2018 . We extracted data on clinical outcomes related to benefits and progression free survival and harms independently by 2 authors . Our search strategy identified 289 references . Five studies were included in this systematic review and meta analysis . Reduced intensity and nonmyeloablative regimens were more commonly prescribed . Mobilized peripheral blood stem cells were the preferred graft source . The pooled OS and PFS rates were 59 50 to 69 and 36 respectively . Pooled relapse rate was 47 and pooled NRM rate 19 . Results of this systematic review and meta analysis show that allo HCT yields encouraging OS and PFS rates however relapse remains a significant cause of allo HCT failure . Novel strategies to further improve outcomes should focus on offering allo HCT before the development of resistant disease and reducing relapse by incorporating post transplant maintenance therapies . | This systematic review and meta analysis demonstrates the efficacy of allo HCT in CTCL. Pooled OS rates of 59 were observed in spite of advanced disease in most cases. A pooled PFS rate of 36 highlights the risk of the disease relapse after allo HCT. |
S1083879119305609 | We analyzed the outcomes of 26 consecutive patients with acquired severe aplastic anemia undergoing peripheral blood stem cell transplantation with partial ex vivo T cell depletion with a targeted T cell dose from HLA identical sibling donors . The median patient age was 37 years . Four patients with uncontrolled pneumonia at the time of transplantation died on days 1 2 21 and 26 . All evaluable patients engrafted with a median time to neutrophil recovery of 11 days and a median time to platelet recovery of 19 days . Two patients had transient grade I acute graft versus host disease with skin involvement but no patients developed grade II IV acute GVHD . Two patients had mild skin chronic GVHD and 1 patient had moderate chronic GVHD with ocular involvement . No relapse was observed after a median follow up of 114 months . The overall cumulative incidence of TRM at 10 years was 19 whereas it was 5 for those with a Karnofsky Performance Status score 60 at the time of transplantation . Disease free survival overall survival and GVHD and relapse free survival at 10 years were 81 81 and 80 respectively for all patients and 95 95 and 90 respectively for patients with a KPS score 60 at transplantation . Our data indicate that PBSCT with partial ex vivo T cell depleted targeted cell dose grafts from an HLA identical sibling donor is a feasible safe and effective approach to reduce GVHD and cure patients with SAA . | PBSCT from HLA identical siblings using partial T cell depletion for patients with SAA is safe and associated with a low incidence of acute GVHD and chronic GVHD. The procedure is effective with high engraftment low TRM and high cure rates. |
S1083879119305610 | Little is known about stem cell transplantation in solid organ transplantation recipients . We conducted a nationwide retrospective survey of Japan Society for Hematopoietic Stem Cell Transplantation centers . A total of 19 patients who underwent 22 hematopoietic stem cell transplantations after SOT were identified 5 autologous HSCTs and 17 allogeneic HSCTs were performed . Patients who underwent autologous HSCT received a liver or kidney transplant . All 5 patients achieved neutrophil engraftment and 2 of 3 patients with hepatoblastoma were alive at 1 year after HSCT . Allogeneic HSCT was performed in 16 patients . Among these 2 donors were identical for both transplantations . All but 1 patient achieved neutrophil engraftment . The 5 year overall survival rate was 41.7 but that in patients with malignant disease was much lower than the overall rate . Only 1 patient with malignant disease underwent allogeneic HSCT in nonremission . In allogeneic HSCT after kidney transplantation post transplantation kidney function in 5 evaluable patients was significantly lower than that before allogeneic HSCT and 3 patients experienced renal rejection . However no severe hepatic rejection was noted . In SOT recipients HSCT is a potentially curable treatment for hematologic disorders but it must be performed with caution especially in patients with malignancy . | A nationwide survey in Japan identified 22 hematopoietic stem cell transplantation HSCT procedures in 19 solid organ transplantation SOT recipients. Successful hematologic engraftment aids HSCT for aplastic anemia after SOT. Disease control before HSCT is crucial in SOT recipients with malignant disease. Renal failure is common and often irreversible in kidney transplant recipients. |
S1083879119305622 | Allogeneic hematopoietic cell transplantation has been increasingly offered to older adults with hematologic malignancies . However optimal methods to determine fitness for alloHCT have yet to be defined . We evaluated the ability of a comprehensive geriatric assessment to predict post alloHCT outcomes in a single center prospective cohort study of patients age 50 years and older . Outcomes included overall survival progression free survival and nonrelapse mortality . A total of 148 patients were included with a median age of 62 years . In multivariate regression analysis several CGA measures of functional status were predictive of post alloHCT outcomes after adjusting for traditional prognostic factors . Any deficit in instrumental activities of daily living was associated with inferior OS 1.81 95 confidence interval 1.07 to 3.08 | Functional status predicts post allogeneic transplantation survival in older patients. Physical function predicts both post allogeneic transplantation survival and toxicity. These associations were independent of age and comorbidities. |
S1083879119305646 | The rationale for in utero hematopoietic cell transplantation rests on exploitation of normal events during hematopoietic and immunologic ontogeny to allow allogeneic hematopoietic engraftment without myeloablative conditioning . Host hematopoietic competition is among the primary barriers to engraftment in IUHCT . In the murine model this can be partially overcome by delivery of larger donor cell doses but volume is limiting . Enrichment of donor hematopoietic stem cells would seem to offer a more efficient approach but such enriched populations have engrafted poorly in existing models of IUHCT . To increase HSC dose while maintaining the presence of accessory cells we used a less stringent enrichment protocol of single step lineage depleted cells alone or in combination with whole donor bone marrow mononuclear cells . Our results confirm that increasing doses of HSCs in combination with bone marrow accessory cells can dramatically improve engraftment after IUHCT . This represents a practical and clinically applicable strategy to maximize the engraftment potential of the donor graft without risk of treatment associated toxicity . | Highly enriched donor cell populations engraft poorly in a murine model of IUHCT. The addition of accessory BM MNC to an enriched population improves engraftment. This is a practical and clinically applicable strategy to increase donor chimerism. |
S1083879119305658 | Transplantation associated thrombotic microangiopathy is an important complication of hematopoietic stem cell transplantation . To date information regarding the organs that are affected by TA TMA as confirmed histologically remains limited the clinicopathologic differences between renal TA TMA and intestinal TA TMA have not been examined despite being the well known and commonly affected sites of TA TMA . We therefore examined 165 autopsied patients after hematopoietic stem cell transplantation and compared the clinicopathologic factors of renal and intestinal TA TMA . It was clear that 38 of our patients had TA TMA . In the TA TMA cases the kidney and intestine were commonly affected and the ileum and right colon were vulnerable . Other organs that we found to be affected by TA TMA included the stomach gallbladder and oral cavity pharynx esophagus liver heart urinary bladder and ureter and symptoms thought to be caused by TA TMA of these organs were not observed in any patient . Histologically TA TMA only affected the arteriole or small arteries regardless of the organ and the veins or larger arteries were not affected at all . In the kidney the glomerular capillary was also affected and mesangiolysis and double contours of the basement membranes were often in evidence . The histologic overlap of renal and intestinal TA TMA was rare and the patients in the intestinal TA TMA group exhibited more frequency of a history of intestinal acute graft versus host disease during the clinical course compared with that of the renal TA TMA group 80 versus 22 | We systemically evaluated transplantation associated thrombotic microangiopathy TA TMA in the largest number of autopsied patients. The kidney and intestine were commonly affected by TA TMA. Many organs were initially histologically confirmed as TA TMA sites. The histologic overlap of renal and intestinal TA TMA was rare at the autopsy. Intestinal TA TMA was more closely associated with a history of intestinal graft versus host disease. |
S108387911930566X | Umbilical cord blood provides an alternative source of hematopoietic stem cells for allogeneic transplantation . Administration of sufficient donor HSCs is critical to restore recipient hematopoiesis and to maintain long term polyclonal blood formation . However due to lack of unique markers the frequency of HSCs among UCB CD34 | Cellular barcodes allow for quantitative longitudinal tracing of human hematopoietic stem cells HSCs in murine recipients. The frequency of HSCs is highly variable between individual cord blood donors. Different analysis methods can cause substantial variation in the number of retrieved clones. |
S1083879119305671 | Bone marrow is a rich source of hematopoietic stem cells mesenchymal stem cells and other important stem progenitor cells . It is the traditional source of cells used in hematopoietic cell transplantation which is a proven curative treatment for many blood and immune diseases . BM derived cells have also been shown to have other diverse clinical uses and are increasingly being used in orthopedic medicine regenerative medicine and gene therapy applications . Traditional methods for harvesting BM are crude tedious time consuming and expensive requiring multiple bone punctures under general anesthesia with serial small volume aspirates often diluted with peripheral blood . The MarrowMiner is a novel device designed for rapid and minimally invasive BM harvest . Here we show the safety and efficacy of the MM in both preclinical and clinical settings . In a large animal porcine model the MM enabled effective BM collection with similar total nucleated cell collection and increased colony formation compared with standard methods . The MM was subsequently evaluated in a clinical study showing effective and complication free anterior and posterior BM collection of 20 patients under only local anesthesia or light sedation . Increased total nucleated and mononucleated cell collection was achieved with the MM compared with standard methods in the same patients . Importantly stem cell content was high with trends toward increased HSC MSC and endothelial progenitor cells with similar T cell content . Given the MM is a novel device approved by the US Food and Drug Administration enabling safe effective and minimally invasive harvest of BM we anticipate rapid adoption for various applications . | MarrowMiner is a safe minimally invasive device for the harvest of bone marrow. MarrowMiner harvests bone marrow without the need for general anesthesia. MarrowMiner collects rich marrow with a high concentration of stem and progenitor cells. |
S1083879119305683 | The use of hematopoietic stem cell transplantation is increasing for a variety of diseases . Ototoxicity from this procedure has not been extensively studied . A retrospective chart review examined 275 patients from this institution who underwent HSCT between January 1 2007 and April 30 2017 . Data extracted included therapy before HSCT and the subsequent course of transplantation . Evaluable patients had complete medical records and interpretable audiograms available . Ototoxicity constituted significant threshold changes from baseline or changes in International Society of Pediatric Oncology Boston Ototoxicity Grading Scale grade comparing audiogram results just before HSCT with those following the transplantation procedure . A total of 147 patients were evaluable . Ototoxicity was observed in 10.2 of the patients . Higher SIOP grade before HSCT was significantly associated with a higher risk of post transplantation ototoxicity | This is the largest series of pediatric HSCT recipients evaluated for ototoxicity reported to date. Ototoxicity was observed in 10 of the patients examined. No type of transplantation was free of ototoxicity. Patients with evidence of hearing loss before the transplantation procedure were at greatest risk. |
S1083879119305695 | Allogeneic hematopoietic stem cell transplantation is a potentially curative treatment for patients with myelodysplastic syndromes and myelodysplastic myeloproliferative neoplasms . However post HSCT relapse remains a major cause of treatment failure . Here we assessed the efficacy of a new conditioning regimen comprising decitabine busulfan cyclophosphamide fludarabine and cytarabine for allo HSCT in patients with MDS and MDS MPN . A total of 48 patients were enrolled including 44 with MDS and 4 with chronic myelomonocytic leukemia . Patients received Dec 20 mg m | Until now decitabine has been used more often for bridge treatment before allogeneic hematopoietic stem cell transplantation allo HSCT or rescue treatment of relapsed myelodysplastic syndrome MDS after transplantation. In this study 5 day decitabine was added for the first time to the conditioning regimen with a satisfactory overall survival OS 86 disease free survival DFS 77 and incidence of graft versus host disease GVHD grade III IV acute GVHD of 23 . Currently the only curative therapy for MDS myeloproliferative neoplasm is allo HSCT but disease recurrence is a major cause of treatment failure after transplantation. In our series we observed only 5 relapses 10 . In particular in the analysis of 25 patients in high extremely high risk groups the 2 year relapse rate and OS were 20 and 78 respectively. All 4 patients who did not achieve complete remission after chemotherapy had DFS after transplantation and the 2 year DFS for 37 patients who had active disease before HSCT was 74 . Among the total 14 patients with poor risk mutations including mutations of. and. only 1 patient 8 with. mutation relapsed and 1 8 with. and. mutations died. In other words patients with mutations associated with poor clinical outcome could benefit more from the condition regimen containing decitabine. To gain more insight into the promising clinical outcomes achieved in our cohort we studied CD3. T cells and CD3. CD16. 56. natural killer NK cells. We found that proper but not excessive levels of NK cells predicted for more benefits to hypomethylating agent conditioning therapy further suggesting the potential use of testing NK cells to predict patient outcomes after allo HSCT. |
S1083879119305701 | Previously reported experimental and clinical data suggest that proteasome inhibition may have immunomodulatory activity relevant to graft versus host disease . To explore the safety and activity of carfilzomib in advanced chronic GVHD we conducted a multicenter pilot phase II trial through the Chronic GVHD Consortium . Carfilzomib was administered at 20 mg m | Once weekly carfilzomib therapy was not well tolerated in patients with advanced chronic GVHD. With limited evidence of efficacy we do not recommend this agent for further study in this indication. |
S1083879119305737 | Uncontrolled studies have suggested that bone marrow derived mesenchymal stem cells may be effective against acute graft versus host disease . We conducted a multicenter randomized study to assess the efficacy of using ex vivo cultured adult human MSC in addition to second line therapy to treat steroid refractory aGVHD . In total 260 patients 6 months to 70 years of age were enrolled from August 2006 to May 2009 and were randomized 2 1 to receive 8 intravenous infusions of remestemcel L or placebo given over 4 weeks in addition to second line therapy according to institutional standards . Four additional infusions over 4 weeks were indicated for patients with incomplete response at day 28 . Randomization was stratified by aGVHD grade . Efficacy and safety were assessed through 180 days of follow up with the primary endpoint being durable complete response defined as complete resolution of aGVHD symptoms for any period of at least 28 days after beginning treatment . Remestemcel L did not meet the primary endpoint of greater DCR in the intent to treat population . In post hoc analyses patients with liver involvement who received at least 1 infusion of remestemcel L had a higher DCR and higher overall complete or partial response rate than those who received placebo . Among high risk patients remestemcel L demonstrated significantly higher OR at day 28 than placebo . Furthermore pediatric patients had a higher OR with MSCs compared with placebo . Similar rates of adverse events were observed between treatment groups . Remestemcel L was safe and well tolerated . Results of this study did not demonstrate superior DCR compared with placebo when added to standard of care . The favorable clinical responses seen in some patient subsets may warrant further investigation . | Mesenchymal stem cells MSC versus placebo added to second line therapy for treatment of steroid refractory acute graft versus host disease aGVHD did not show benefit. MSC infusions were well tolerated and did not result in excess adverse events compared with placebo. Post hoc subgroup analyses suggested favorable odds of day 28 response in children and in patients with high risk aGVHD or liver involvement. |
S1083879119305750 | Post autologous stem cell transplantation maintenance therapy with lenalidomide is standard of care for patients with multiple myeloma . Effective and tolerable drug combinations may further enhance the clinical response post ASCT . Vorinostat a histone deacetylase inhibitor induces antiproliferative and proapoptotic effects in patients with MM . We hypothesized that combination maintenance therapy would further prolong the clinical response achieved from transplantation . We previously reported that the combination of lenalidomide and vorinostat as maintenance post ASCT was tolerable in 16 patients with MM . We now present the long term follow up of these patients . Progression free survival and overall survival outcomes were characterized using the Kaplan Meier method . Five patients had high risk disease and the median number of lines of therapy before ASCT was 1 . With a median follow up of 89.8 months from ASCT the median PFS was 64.3 months and OS was not reached . At the time of this report 5 patients remained on the study . The combination of vorinostat and lenalidomide as maintenance post ASCT is tolerable and induces a durable response . A phase III randomized study of lenalidomide versus a combination with vorinostat is warranted . | The combination of vorinostat and lenalidomide as maintenance post transplantation is tolerable and induces durable response. With a median follow up of 89.8 months from autologous stem cell transplantation the median progression free survival was 64.3 months range 21.7 months to not reached NR and overall survival was not reached range 53.0 months to NR . The use of lenalidomide plus vorinostat could prove to be a promising maintenance strategy in patients with newly diagnosed multiple myeloma. |
S1083879119305762 | Molecular data and minimal residual disease have been shown to influence outcomes in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation . Here we developed and validated a novel AML specific disease risk group and revised our previously developed hematopoietic cell transplant composite risk model by incorporating molecular data and MRD status to predict outcomes of patients with AML . The study included 1414 consecutively treated adult AML patients who received a first AHCT . Patients were randomly assigned into training and validation sets . To develop the AML DRG model the coefficient of all significant AML related variables in multivariable Cox regression analysis in a training dataset was converted into scores whereas the AML HCT CR was the sum of disease related factors assessed by the AML DRG model with the addition of weighted scores from patient related factors . The AML DRG was developed by assigning the following scores 1 point to secondary AML 1 point to the European LeukaemiaNet adverse genetic risk 2 points to complete remission with MRD positive unknown and 4 points to active disease . These scores were used to generate 3 risk groups of the AML DRG with significantly different overall survivals . By adding the score for significant patient related factors we created 4 risk groups of AML HCT CR with distinct survival outcomes . Both the AML DRG and AML HCT CR provided significantly better discriminative capacity compared with the disease risk index European LeukaemiaNet genetic risk model and cytogenetic risk model . Prognostic models incorporating molecular data and MRD status allow better stratification and improved survival estimates of AML patients post transplant . | Molecular data and MRD at transplant for AML patients significantly influence outcomes. By incorporating these factors we developed an AML DRG which has improved predictive ability compared with the DRI. A risk model combining patient and disease related factors the HCT CR effectively predicts OS for AML. The AML HCT CR divides patients into 4 groups with significantly different post transplant survival. |
S1083879119305932 | High dose chemotherapy followed by autologous hematopoietic stem cell transplantation improves survival in patients with chemosensitive non Hodgkin lymphoma . Determination of the Hematopoietic Cell Transplantation Comorbidity Index has contributed to improve patient selection while allowing for prediction of nonrelapse mortality . We previously demonstrated the efficacy and safety of AHSCT in a cohort of older patients with chemosensitive NHL . Quality of life following AHSCT still has not been widely evaluated . The goal of this study was to assess the long term quality of life of elderly patients surviving AHSCT . This single center Research and Ethics Committee approved study investigated QoL in survivors of AHSCT for the treatment of NHL in a cohort of older patients . Inclusion criteria were defined as patients age 60 years who underwent AHSCT for NHL between January 1 2008 and January 1 2015 at our center . Fifty nine patients from the original cohort of 90 survived at a median of 50 months post AHSCT . Forty seven of those patients agreed to complete the QoL assessment questionnaires after the transplantation and are included in this report . All patients provided signed informed consent . We used the EQ 5D instrument to assess mobility self care usual activities pain discomfort and anxiety depression and the Functional Assessment of Cancer Therapy Bone Marrow Transplant questionnaire to assess physical social family emotional and functional well being and BMT specific concerns . With both tools a higher score indicates better QoL . Fifteen percent of patients were in relapse at the time of the QoL assessment . In the EQ 5D few patients reported severe impairment which requires significant negative effects in 4 or 5 domains . Lower Karnofsky Performance Status score at the time of transplantation was negatively correlated with mobility | Quality of life is well preserved after autologous hematopoietic stem cell transplantation AHSCT in older patients. Relapse remains one of the main challenges affecting quality of life. Self care is the least affected area after undergoing AHSCT. Older patients should not be excluded from AHSCT based solely on their age. |
S1083879119305944 | The high cost of healthcare in the United States has not been consistently associated with improved health outcomes or quality of care necessitating a focus on value based care . We identified busulfan dosing frequency during allogeneic hematopoietic cell transplantation conditioning as a potential target for optimization . To improve patient convenience and to decrease the cost of busulfan based conditioning regimens our institution changed busulfan dose frequency from every 6 hours to once daily . We compared costs and patient outcomes between these 2 dosing schedules . In June 2017 our institution transitioned from q6h to q24h busulfan dosing . We compared patients who received busulfan cyclophosphamide conditioning regimens for allogeneic HCT in the year before the dosing change and those who did so in the year after the dosing change . The primary outcomes were differences in cost day 90 mortality and day 90 relapse . Between June 1 2016 and June 1 2018 104 patients received BU CY before allogeneic HCT . Fifty nine patients received q6h busulfan and 45 received q24h busulfan . There were fewer men in the q24h busulfan cohort compared with the q6h busulfan cohort 42 versus 64 | Every 24 hour q24h dosing of i.v. busulfan reduced drug waste compared with every 6 hour q6h dosing. Reduced busulfan drug waste led to a cost savings of nearly 20 000 USD per patient. Clinical outcomes were equivocal or improved with q24h dosing compared with q6h dosing. |
S1083879119305956 | Induced pluripotent stem cells have been applied to clinical regenerative cell therapy . Recently an iPSC banking system to collect HLA haplotype homozygous cells for iPSC transplantation in allogeneic settings was proposed and tissue transplantation generated from iPSC through banking has just began . We analyzed 5017 single cord blood transplantation pairs with HLA A B C DRB1 allele typing data and found 39 donor HLA homo donor to patient HLA heterozygous pairs . Of note all 39 HLA homo to hetero pairs engrafted neutrophils except 1 early death pair and all 30 assessable pairs engrafted platelets . Acute graft versus host disease grades II to IV and grades III to IV occurred in 17 and 3 of 38 assessable pairs respectively . Competing risk regression analysis revealed a favorable risk of neutrophil engraftment and higher risk of acute GVHD compared with HLA matched CBTs . Thirty seven of 39 homo to hetero pairs had conserved extended HLA HPs that were ethnicity specific and at least 1 of 2 patient HLA A B C and DRB1 alleles in each locus were invariably shared with the same donor HP in 35 pairs . These findings confirmed our preliminary results with 6 HLA homo CBTs and a trend of high incidence of acute GVHD was newly observed . Importantly they imply the possibility that HLA homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major conserved extended HLA HPs . | All assessable patients with donor HLA homo to patient HLA hetero pairs among 5017 single CBT pairs were engrafted neutrophil 38 pairs and platelets 30 pairs and revealed a tendency of high incidence of acute GVHD. Ethnicity specific conserved extended HLA haplotypes CEHs were invariably shared with the same donor HP in 35 pairs. These findings imply the possibility that HLA homo iPSC transplantation provides favorable engraftment and accordingly imply the merit of banking iPSC with homozygous major CEHs. |
S1083879119305968 | Little is known about the inflammatory milieu in the blood during autologous hematopoietic stem cell transplantation and how it is affected by the stem cell mobilization collection and reinfusion and conditioning regimen . In this study we analyzed 92 proteins connected to inflammation at 10 time points during and after AHSCT in 16 patients with multiple sclerosis . Serum from 29 patients with newly diagnosed MS and 15 healthy controls were included for comparative analysis . There were no significant differences in inflammatory serum protein levels between patients with newly diagnosed MS and healthy controls but 29 out of 73 detectable proteins were significantly altered between at least 2 adjacent sampling time points during AHSCT . The predominant changes occurred after the conditioning regimen had been administered whereas stem cell mobilization collection and reinfusion appeared to have less impact . Two distinct response patterns could be discerned likely representing loss of basal cytokine production and homeostasis . The analyzed serum proteins gradually returned to baseline levels after treatment with no remaining differences at 3 months after AHSCT . We conclude that treatment with AHSCT has a major but transient impact on the inflammatory milieu of peripheral blood . | Inflammatory serum proteins are profoundly altered by conditioning regimen for autologous hematopoietic stem cell transplantation AHSCT . Two distinct patterns of serum proteins are distinguished during AHSCT. There are no visible effects of MS disease activity on inflammatory serum proteins. Serum protein levels are normalized by 3 months after AHSCT. |
S1083879119306263 | The third annual Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Workshop on Minimal Residual Disease and Immune Profiling was held on November 29 2018 at the American Society of Hematology annual meeting . This workshop featured the latest research focused on minimal residual disease assessment and immune profiling in myeloma as well as discussion of the statistical and regulatory issues intrinsic to the development of MRD as a surrogate endpoint . In this report we provide a summary of the workshop and focus on the integration of MRD and IP assessment into trial design and clinical practice . | This is a comprehensive summary from the third annual Blood and Marrow Transplant Clinical Trials Network Myeloma Intergroup Minimal Residual Disease MRD and Immune Profiling IP workshop. MRD is not yet established as a surrogate endpoint but is a prognostic biomarker. Incorporation of IP as an exploratory endpoint in trial design is recommended. |
S1083879119306275 | To prospectively validate the incidence manifestations and outcomes of graft versus host disease by National Institutes of Health criteria we recruited 406 hematopoietic stem cell transplantation recipients at 16 transplant centers in Japan from May 2012 to June 2014 . The 2 year cumulative incidence of late acute and chronic GVHD was 3.2 and 35.4 with a median onset of 3.6 and 4.7 months after transplant respectively . The global severity at onset was mild in 30.3 moderate in 43.5 and severe in 26.2 . Eighty two patients were followed up for 2 years with 79.3 still manifesting GVHD symptoms and 80.6 of the patients received systemic immunosuppressive treatment with a 2 year cumulative incidence of IST termination of 33.1 . Severe patients showed a significantly lower rate of IST termination than those with mild and moderate severities . The 2 year incidence of nonrelapse mortality and relapse was not significantly different according to the severity at onset versus moderate versus severe relapse mild versus moderate versus severe . As a result 2 year overall survival and GVHD specific survival were equivalent according to the severity at onset . Our study helped identify the characteristics of late acute and chronic GVHD in Japanese patients . Further investigation is needed to identify an optimal endpoint for survival prediction . | The incidences of late acute and chronic graft versus host disease GVHD were lower in Japanese than in whites. Organ manifestations and risk factors were similar to previous reports. Global severity was not associated with overall survival nonrelapse mortality or GVHD specific survival. Severe patients showed a significantly lower rate of treatment termination. |
S1083879119306287 | Cyclophosphamide etoposide combined with fractionated total body irradiation or i.v . busulfan has been the main conditioning regimens for allogeneic hematopoietic cell transplantation for young patients with acute myelogenous leukemia eligible for a myeloablative conditioning regimen . Recent data has suggested that i.v . Bu could be the preferred myeloablative regimen in patients with myeloid malignancies . However Bu based regimens are associated with higher rates of sinusoidal obstruction syndrome . Here we report long term survival outcomes of patients with AML receiving FTBI combined with Cy or etoposide before undergoing alloHCT at City of Hope . We obtained a retrospective review of a prospectively maintained institutional registry of clinical outcomes in 167 patients with AML in first or second complete remission who underwent alloHCT at COH between 2005 and 2015 . Eligible patients received a MAC regimen with FTBI and Cy for unrelated donor transplantation or etoposide for related donor transplantation . Graft versus host disease prophylaxis was provided with tacrolimus and sirolimus . In this retrospective study 6 year overall survival was 60 and nonrelapse mortality was 15 . The GRFS rate was 45 at 1 year and 39 at 2 years . We also describe late metabolic effects and report the cumulative incidence of secondary malignancies . Overall in this young adult patient population our results compare favorably to chemotherapy based conditioning regimens without significant long term toxicity arising from TBI based regimens . | Fractionated total body irradiation based myeloablative conditioning is well tolerated in young adults with acute myelogenous leukemia. Tacrolimus sirolimus graft versus host disease GVHD prophylaxis was associated with high rates of chronic GVHD 71 . GVHD free relapse free survival at 2 years was low 39 indicating the dynamic nature of chronic GVHD. This regimen was associated with a low risk of long term toxicities. |
S1083879119306329 | Almost comparable transplantation outcomes have been reported with HLA matched unrelated donor transplantation and cord blood transplantation . We conducted a prospective phase 2 study to assess the efficacy and safety of single unit myeloablative CBT in adult leukemia and myelodysplastic syndrome . Because the day 180 survival of UDT was approximately 80 we determined the alternative hypothesis of expected day 180 survival with a successful engraftment rate of 80 and set the null hypothesis of threshold rate at 65 . Sixty two patients were registered including 28 with acute myelogenous leukemia 25 with acute lymphoblastic leukemia and 9 with myelodysplastic syndrome . Of 61 eligible patients 52 were successfully engrafted and survived at day 180 . Single unit CBT was judged to be effective because the null hypothesis was rejected | We conducted a phase 2 single arm prospective study of cord blood transplantation CBT . We assessed the efficacy of CBT for treating patients with adult acute leukemia and myelodysplastic syndrome. CBT showed significantly better day 180 overall survival than threshold survival. CBT outcomes are comparable to historical unrelated donor transplantation in adults with low comorbidity. Patients with high risk features in complete response status may benefit from early CBT. |
S1083879119306342 | FLT3 ITD mutated acute myeloid leukemia remains a therapeutic challenge . FLT3 inhibition in the setting of minimal residual disease and a new immune system via allogeneic transplantation offers a promise of improved survival for these patients . We performed a prospective study of patients with FLT3 ITD AML undergoing allogeneic transplant that was conducted to evaluate the safety tolerability and outcome of sorafenib administered peritransplant . Sorafenib dosing was individualized starting at 200 mg twice a day and titrated based on tolerability or toxicities until a tolerable dose was identified . Forty four patients with a median age of 52 years undergoing allogeneic transplant were started on sorafenib in the peritransplant period . The median duration of post transplant follow up was 27.6 months . Overall survival was 76 at both 24 and 36 months . Event free survival at 24 and 36 months was 74 and 64 respectively . Ten patients died in the post transplant period with 6 deaths due to relapsed leukemia and 4 from transplant associated toxicity . Tolerable doses ranged from 200 mg every other day to 400 mg BID with similar exposure . Correlative studies evaluating FLT3 inhibition via a plasma inhibitory activity assay showed consistent inhibition of FLT3 at all tolerability determined dosing levels . Sorafenib is well tolerated in the peritransplant setting irrespective of the conditioning intensity or the donor source . Our findings indicate that sorafenib dosing can be individualized in the post transplantation setting according to patient tolerability . This approach results in effective in vivo FLT3 inhibition and yields encouraging survival results . | Sorafenib is safe and well tolerated before and after transplant if dosed according to patient adverse effects. Sorafenib use after transplant is associated with encouraging post transplant survival in patients with FLT3 ITD acute myeloid leukemia undergoing hematopoietic stem cell transplant. Sorafenib dosing according to patient tolerance achieves target suppression of FLT3 ITD. |
S1083879119306354 | The Predicted Indirectly Recognizable HLA Epitopes score quantifies the number of PIRCHEs in patient donor pairs and represents an in silico measure of indirect alloreactivity . This biologic process is defined as T cell recognition of epitopes derived from mismatched allogeneic HLA peptides that are subsequently presented by shared HLA molecules . Its association with clinical outcome has not been examined in haploidentical hematopoietic cell transplantation with post transplantation cyclophosphamide . We hypothesized that the PIRCHE score would correlate with indirect alloreactivity and predict graft versus host disease risk and the incidence of relapse after haplo HCT with PTCy . We retrospectively analyzed 148 patients who underwent peripheral blood stem cell T cell replete haplo HCT with PTCy at a single center between 2009 and 2016 . For each patient donor pair the PS was calculated using the PIRCHE online matching tool . PSs were categorized by class and vector . The median class I graft versus host PS was 11 and the median class I host versus graft PS was 10 . Class I GVH PS was associated with increased risk of grade II IV acute GVHD adjusted hazard ratio 1.03 per PS unit increase 95 confidence interval 1.01 to 1.05 | PIRCHE scores offer a method of quantifying indirect T cell alloreactivity. PIRCHE scores offer a broad range of measurement of HLA disparity. Graft versus host PIRCHE scores correlate with acute graft versus host disease. PIRCHE scores may improve donor selection in haploidentical transplantation. |
S1083879119306366 | The optimal intensity of conditioning regimen may be dependent on not only age and comorbidities but also disease characteristics and risk of relapse after allogeneic hematopoietic cell transplantation . We therefore analyzed the transplant outcomes of 840 adult patients with cytogenetically poor risk acute myeloid leukemia in first complete remission who received first allogeneic HCT with either myeloablative conditioning or reduced intensity conditioning between 2006 and 2017.The median age at HCT was 50.5 years . The multivariate analysis showed that patients receiving MAC had a significantly higher overall survival and lower leukemia related mortality than those receiving RIC | In comparison with reduced intensity conditioning myeloablative conditioning MAC reduced leukemia related mortality and improved overall survival for patients with cytogenetically poor risk acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation HCT during first complete remission. In the subgroup analysis these results applied to patients aged 16 to 59 years with HCT comorbidity index scores 3 and with cytogenetic remission. Among MAC regimens there was a trend for worse survival and nonrelapse mortality with the busulfan fludarabine based regimen compared with the total body irradiation based regimen. |
S1083879119306378 | Patients undergoing hematopoietic stem cell transplantation are often admitted to the hospital the day they are due to begin their conditioning regimen . Timely initiation of chemotherapy during regular work hours is important for patient safety because during the night shift fewer physicians and pharmacists are available for urgent or unexpected matters . A review of the data at our institution from October 2017 to August 2018 showed that approximately one third of our chemotherapy was started during the night shift and the average time from admission to start of chemotherapy was over 8 hours . There are currently no well defined benchmarks for timeliness of chemotherapy initiation . The aim of this quality improvement initiative was to increase the percentage of patients who start chemotherapy in the bone marrow transplant unit before 19 00 from 65 to 80 by March 31 2019 . We identified barriers to timely initiation of chemotherapy through process mapping and analysis of failures . The primary barriers were late admissions and time from admission to preparation of chemotherapy . We addressed mechanisms to mitigate these barriers through Plan Do Study Act testing . Interventions included providing families specific admission times and their rationales and process for notifying pharmacy of admissions immediately on arrival . We used standardized control charts to measure the impact of the interventions on change . We also monitored medication errors before and during the intervention . From September 2018 to March 2019 the percentage of patients who started preparative chemotherapy before 19 00 increased from 65 to 85 the percentage of patients who were admitted after 12 00 remained similar before and after the interventions and the average time from admission to start of chemotherapy decreased from 8.6 hours to 6.4 hours . Medication errors were similar before and after the interventions . Using standardized processes we demonstrated a substantial decrease in the percentage of HSCT patients starting their preparative regimen after 19 00 without a concurrent increase in errors . We believe these interventions and measurements can be used in all transplant centers and have the potential to influence patient safety and outcomes . | Initiating chemotherapy during regular work hours is important for patient safety. Barriers to this are late admissions and time from admission to chemotherapy administration. Providing families with specific admission times and rationale improved admission times. Prompt nursing and pharmacy communication decreased time to chemotherapy. This multidisciplinary approach improved timeliness of chemotherapy administration. |
S108387911930638X | Critically ill pediatric allogeneic hematopoietic cell transplant patients may benefit from early and aggressive interventions aimed at reversing the progression of multiorgan dysfunction . Therefore we evaluated 25 early risk factors for pediatric intensive care unit mortality to improve mortality prognostication . We merged the Virtual Pediatric Systems and Center for International Blood and Marrow Transplant Research databases and analyzed 936 critically ill patients 21 years of age who had undergone allogeneic HCT and subsequently required PICU admission between January 1 2009 and December 31 2014 . Of 1532 PICU admissions the overall PICU mortality rate was 17.4 15.6 to 19.4 but was significantly higher for patients requiring mechanical ventilation renal replacement therapy or extracorporeal life support . Mortality estimates increased significantly the longer that patients remained in the PICU . Of 25 HCT and PICU specific characteristics available at or near the time of PICU admission moderate severe pre HCT renal injury pre HCT recipient cytomegalovirus seropositivity 100 day interval between HCT and PICU admission HCT for underlying acute myeloid leukemia and greater admission organ dysfunction as approximated by the Pediatric Risk of Mortality 3 score were each independently associated with PICU mortality . A multivariable model using these components identified that patients in the top quartile of risk had 3 times greater mortality than other patients 35.1 versus 11.5 | Critically ill pediatric allogeneic hematopoietic cell transplant HCT patients may benefit from early and aggressive interventions aimed at reversing the progression of multiorgan dysfunction. Using a multicenter cohort of 936 critically ill pediatric allogeneic HCT patients across 77 intensive care units this study identified that pre HCT renal injury pre HCT cytomegalovirus seropositivity acute myeloid leukemia Both myeloid and myelogenous are acceptable post HCT day and a continuous metric of multiorgan dysfunction the Pediatric Risk of Mortality 3 score prognosticated pediatric intensive care unit mortality for the highest risk patients. A multivariable model using these components identified that patients in the top quartile of risk had 3 times greater mortality than other patients 35.1 versus 11.5. .001 . |
S1083879119306391 | Cytomegalovirus reactivation and natural killer cell reconstitution are well recognized immunologic events occurring after allogeneic stem cell transplantation . We aimed to study the outcome of CMV reactivation and NK cell reconstitution in patients with hematologic malignancies after allo SCT . We retrospectively studied 246 adult patients who underwent allo SCT for hematologic malignancies at the Kanagawa Cancer Center . CMVR was defined as initiation of preemptive CMV therapy after pp65 antigenemia surveillance . All patients lymphocyte subsets were monitored by flow cytometry at 180 365 and 730 days post transplant . The median follow up period was 3.2 years . CMVR occurred in 141 patients at a median of 45 days . In patients without CMVR versus those with CMVR 5 year overall survival nonrelapse mortality and cumulative incidence of relapse were 79 versus 55 | Post transplant cytomegalovirus CMV reactivation is associated with nonrelapse mortality and overall survival. A natural killer NK cell subset significantly contributed to a lower cumulative incidence of relapse. NK cell reconstitution improved post transplant outcomes especially in patients with CMV reactivation. |
S1083879119306470 | An open label phase 2 study of topical dexamethasone versus tacrolimus solutions in new onset oral chronic graft versus host disease revealed the superior efficacy of dexamethasone . The objective of this study was to report long term patterns of topical therapy utilization and clinical outcomes in this cohort after completing the 30 day trial . A retrospective record review was performed from the date of study completion to January 2017 . Topical therapies systemic immunosuppressive therapies objective measurements patient reported outcomes and adverse events were recorded for oral cGVHD related outpatient visits . Follow up periods were defined as FU1 FU2 FU3 FU4 FU5 and FU6 . Forty patients completed the clinical trial and were included in the analysis . Topical therapies used were dexamethasone tacrolimus clobetasol or a combination of these agents . At FU1 all 40 patients were receiving topical therapy which decreased to 54.5 at FU6 . Clinician reported oral mucosal scores and patient reported sensitivity scores decreased over time from FU1 to FU6 . Intralesional steroid therapy was provided to 6 patients for management of refractory oral ulcerations all within the first year of follow up . Patients with de novo symptomatic oral cGVHD may require long term care with topical immunomodulatory therapy for up to 2 years if not longer . Topical steroid and tacrolimus therapies are safe and effective in managing symptomatic oral cGVHD . Second line topical therapy for refractory oral cGVHD requires further investigation . | More than 40 of patients were still being treated with topical therapy for oral chronic graft versus host disease cGVHD at 24 months after the initiation of oral topical therapy. Topical therapies were often switched between follow ups. Clinician reported National Institutes of Health oral mucosal score 0 12 median improved from 3 at 1 month to 1 at 24 months. Patient reported sensitivity score 0 10 median improved from 3 at 1 month to 2 at 6 months. Additional studies are warranted for long term utilization of topical therapies in oral cGVHD. |
S1083879119306482 | Post transplantation cyclophosphamide reduces the risks of severe acute and chronic graft versus host disease after allogeneic hematopoietic cell transplantation . Yet the standard clinical dose and timing of PTCy were partly extrapolated from MHC matched skin allografting models and were partly empirical . Here we investigated the impact of differential dosing and timing of PTCy on its efficacy in preventing GVHD in a murine MHC haploidentical HCT model . Administration of PTCy on days 3 4 was superior to administration on days 1 2 5 6 or 7 8 whereas low dose PTCy on days 1 2 actually led to accelerated death . Although the optimal timing of PTCy dosing was day 2 or 3 in the skin allografting models in our MHC haploidentical HCT model PTCy on days 2 3 was inferior to PTCy on days 3 4 at lower doses . PTCy administered on days 3 4 4 5 or 3 5 were similarly efficacious . Single day versus 2 day dosing schedules demonstrated that PTCy is maximally effective when given on day 4 . Flow cytometric analysis showed that optimal PTCy dosing schedules both decreased alloreactive CD4 | The dose timing and cumulative exposure of post transplantation cyclophosphamide all are critical for its efficacy. The maximal efficacy of post transplantation cyclophosphamide peaks at day 4. Effective dosing schema reduce alloreactive conventional CD4. T cell proliferation and allow preferential regulatory T cell recovery. |
S1083879119306512 | Allogeneic hematopoietic stem cell transplantation can be curative for patients with hematologic malignancies . The ideal conditioning regimen before allo HSCT has not been established . We conducted a Phase II study to evaluate the tolerability and efficacy of clofarabine and treosulfan as conditioning regimen before allo HSCT . The primary objective was to evaluate the cumulative incidence of nonrelapse mortality on day 100 . Forty four patients were enrolled . The median patient age was 47 years and the median duration of follow up was 27 months . The conditioning regimen was based on clofarabine 40 mg m | This Phase II study evaluated the tolerability and safety of a clofarabine and treosulfan conditioning regimen before allogeneic hematopoietic stem cell transplantation. We found a low incidence of severe hepatic toxicities such as veno occlusive disease. Disease relapse represent a major issue mainly for patients with poor prognostic risk factors. |
S1083879119306524 | Optimal administration of busulfan is hampered by variable and unpredictable drug metabolism in individual patients . At our institution Bu was previously administered with fixed weight based dosing in combination with cyclophosphamide and etoposide for patients with non Hodgkin lymphoma undergoing autologous stem cell transplantation . In 2014 we adopted real time pharmacokinetic guided therapeutic drug monitoring of Bu for all NHL patients undergoing Bu containing ASCT . Here we compare outcomes of NHL patients who underwent ASCT with Bu Cy E using WBD and those who did so using TDM of Bu . We studied 336 consecutive adult NHL patients who underwent ASCT with Bu Cy E using WBD from January 2007 to December 2013 or TDM from May 2014 to December 2017 excluding patients with mantle cell lymphoma . Clinical outcomes including relapse nonrelapse mortality progression free survival and overall survival hepatotoxicity and pulmonary toxicity were compared in the 2 groups . To adjust for differences in baseline characteristics between the groups propensity matched cohorts of WBD and TDM patients were also studied . After the first dose of Bu the dose was increased in 36 of the patients and decreased in 41 . Changes in pulmonary and liver function from baseline to transplantation were not different between the 2 groups although these changes showed significantly less variability with TDM than with WBD . Relapse was significantly lower and PFS was improved with TDM 2 year estimates were 19 for TDM and 38 for WBD for relapse | Previous studies have shown that pharmacokinetic PK directed therapeutic dose monitoring TDM of i.v. administered busulfan results in a larger proportion of patients receiving desired busulfan exposure. Comparison of PK directed dosing of busulfan as part of preparative regimen for autologous stem cell transplantation ASCT did not appear to improve outcomes of historical controls with non Hodgkin lymphoma NHL treated with standard BEAM chemotherapy but a prospective trial showed improved relapse and nonrelapse morality in patients with AML MDS undergoing allogeneic stem cell transplantation with PK directed versus weight based dosing of busulfan. In the present study of sequential cohorts of patients with NHL undergoing ASCT using weight based dosing or TDM of busulfan we found improvements in relapse rates and progression free survival using TDM. |
S1083879119306536 | Although autologous hematopoietic cell transplantation is standard therapy for patients with lymphoma and multiple myeloma few studies have addressed late effects and quality of life in long term survivors after AHCT . Using long term follow up annual questionnaires with self reported outcomes we surveyed 665 patients who were at 5 years after AHCT for the diagnosis of lymphoma or MM . Three hundred and eighty nine patients completed the questionnaire at a median of 11 years after AHCT . The median patient age was 63 years in the 268 patients with lymphoma and 69 years in the 121 patients with multiple myeloma . The most commonly reported medical conditions were sexual dysfunction history of shingles cataracts osteoporosis or osteopenia joint replacement and skin cancer . Current medication use was more frequent in the patients with MM for infection prevention treatment 19 for MM versus 5 lymphoma | Patient undergoing autologous hematopoietic cell transplantation AHCT for lymphoma reported better health and quality of life QoL compared with those undergoing AHCT for multiple myeloma. At a median of 11 years after AHCT we identified important late effects and QoL deficits that are potentially amenable to intervention. |
S1083879119306548 | Our current knowledge of idiopathic pneumonia syndrome predates improved specificity in the diagnosis of IPS and advances in hematopoietic cell transplantation and critical care practices . In this study we describe and update the incidence risk factors and outcomes of IPS . We performed a retrospective cohort study of all adults who underwent allogeneic HCT at the Fred Hutchinson Cancer Research Center between 2006 and 2013 . IPS was defined using the National Heart Lung and Blood Institute consensus definition multilobar airspace opacities on chest imaging absence of lower respiratory tract infection and hypoxemia . We described IPS incidence and mortality within 120 and 365 days after HCT . We examined conditioning intensity versus myeloablative with low dose TBI as an IPS risk factor in a time to event analysis using Cox models controlled for age at transplant HLA matching stem cell source and pretransplant Lung function Score a combined measure of impairment in Forced Expiratory Volume in the first second FEV | The incidence of idiopathic pneumonia syndrome IPS is declining in a modern cohort of allogeneic hematopoietic cell transplantation HCT recipients. Total body irradiation dose remains a significant risk factor for IPS development. IPS is a rare but substantial cause of post HCT morbidity and mortality. |
S108387911930655X | It remains unclear whether the HLA haplotype of unrelated cord blood should be matched to that of the patient in single UCB transplantation . Thus using data from a Japanese registry we analyzed the effect of haplotype matching on outcomes . Patients with hematologic diseases aged 16 years or older who had undergone their first transplant were included . The effects of haplotype matching and high frequency HLA haplotype on outcomes were analyzed . Median patient age was 55 years . The cumulative incidences of neutrophil engraftment among groups with 0 1 and 2 HLA haplotype matches were 79 82 and 88 respectively | It is better to match the HLA haplotype to improve neutrophil and platelet engraftment in single UCBT. Two haplotype matches should be avoided if the relapse risk is high. The haplotype itself may have an effect on the risk of acute GVHD and relapse after UCBT. |
S1083879119306561 | This study aimed to investigate time varying effects of graft type on outcomes for patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplant . For this purpose we analyzed 3952 patients 720 of whom underwent matched related bone marrow transplantation 1004 matched related peripheral blood stem cell transplantation 856 matched unrelated BMT and 1372 umbilical cord blood transplantation during complete remission . The 4 year relapse free survival rates were 59.1 52.8 59.5 and 50.6 respectively . Compared with related BMT related PBSCT unrelated BMT and UCBT were associated with higher risk of nonrelapse mortality and unrelated BMT and UCBT with lower risk of relapse . As a result both RFS and overall survival were comparable between related BMT and unrelated BMT but were worse for related PBSCT and UCBT than for related BMT . Adverse impact of UCBT was observed only during the early phase of transplant whereas that of related PBSCT continued even after 2 years post transplant . Our findings raise concerns about the increased risk of late nonrelapse mortality with the use of PBSC grafts and suggest that related BMT is preferable to related PBSCT matched unrelated BMT is the next choice in the absence of a matched related donor . | This study aimed to investigate time varying effects of graft type on allogeneic HCT outcomes for AML. RFS and OS were worse for related PBSCT and UCBT than for related BMT. Adverse impact of UCBT was observed only during the early phase of transplant. Adverse impact of related PBSCT continued even after 2 years post transplant. Our findings raise concerns regarding the increased risk of late nonrelapse mortality with the use of PBSC grafts. |
S1083879119306573 | CD19 targeted chimeric antigen receptor modified T cell immunotherapy is a novel treatment with promising results in patients with relapsed refractory lymphoid malignancies . CAR T cell therapy has known early toxicities of cytokine release syndrome and neurotoxicity but little is known about long term neuropsychiatric adverse effects . We have used patient reported outcomes including Patient Reported Outcomes Measurement Information System measures to assess neuropsychiatric and other patient reported outcomes of 40 patients with relapse refractory chronic lymphocytic leukemia non Hodgkin lymphoma and acute lymphoblastic leukemia 1 to 5 years after treatment with CD19 targeted CAR T cells . Mean T scores of PROMIS domains of global mental health global physical health social function anxiety depression fatigue pain and sleep disturbance were not clinically meaningfully different from the mean in the general US population . However 19 patients reported at least 1 cognitive difficulty and or clinically meaningful depression and or anxiety and 7 patients scored 40 in global mental health indicating at least 1 standard deviation worse than the general population mean . Younger age was associated with worse long term global mental health | Overall long term survivors after chimeric antigen receptor CAR T cell therapy report good mental health. A subset of patients may experience psychiatric symptoms or cognitive impairment. Allogeneic hematopoietic cell transplantation before or after CAR T cells does not affect long term mental health. Older age is associated with better mental health in long term CAR T cell survivors. Cognitive difficulties are associated with worse global mental and physical health. |
S1083879119306597 | Large series of patients with acute myelogenous leukemia after ex vivo T cell depleted allogeneic hematopoietic stem cell transplantation have not been reported previously . We retrospectively analyzed the outcomes of 266 patients with AML who received CD34 selected TCD allo HSCTs while in first or second complete remission at a single institution . The conditioning regimens were all myeloablative and no additional graft versus host disease prophylaxis was given . The cumulative incidences of grade II IV and grade III IV acute GVHD at 180 days were 14 10 to 18 and 3 respectively . The cumulative incidence of chronic GVHD at 3 years was 3 . The 3 year cumulative incidence of nonrelapse mortality was 21 and that of relapse was 21 . Overall survival and disease free survival at 1 3 and 5 years were 75 61 and 56 and 68 57 and 53 respectively . There were no significant differences in OS DFS and relapse rates for patients who underwent transplantation in CR1 and those who did so in CR2 . However patients with high risk cytogenetics at diagnosis had significantly poorer outcomes . The OS and DFS rates compare favorably with those for unmodified allo HSCT but with considerably lower rates of GVHD . | Ex vivo T cell depleted TCD hematopoietic stem cell transplantation HSCT in patients with acute myelogenous leukemia AML in first or second complete remission CR1 CR2 is associated with comparable overall survival and disease free survival to unmodified HSCT. Transplantation outcomes are similar in patients with AML CR1 CR2 following TCD HSCT. The risk of relapse after ex vivo TCD HSCT is no higher than after unmodified HSCT. Ex vivo TCD HSCT is associated with a significantly lower rate of graft versus host disease compared with unmodified HSCT. |
S1083879119306603 | Mixed chimerism and or secondary graft failure with recipient or donor type chimerism is a major obstacle in allogeneic transplantation for aplastic anemia . From a registry database in Japan patients with AA age 15 years who underwent a first allogeneic bone marrow or peripheral blood stem cell transplantation between 2000 and 2014 and achieved engraftment were included in this study . MC that did not require either granulocyte colony stimulating factor or transfusion support MC that required G CSF and or transfusion support SGF with MC or complete recipient type chimerism and SGF with complete donor type chimerism developed in 26 16 19 and 17 patients respectively . The overall median duration of follow up for survivors was 1727 days . The overall survival was 90.4 at 1 year and 83.5 at 5 years in patients without MC or SGF which was not different from the OS in groups 1 and 2 . However inferior OS was observed in group 3 and group 4 . In multivariate analyses the use of fludarabine and the absence of irradiation in conditioning were associated with the development of SGF with MC or complete recipient type chimerism and the use of Flu in conditioning was associated with SGF with complete donor type chimerism . In conclusion the use of Flu may affect the occurrence of SGF with both recipient type and donor type chimerism . | The influence of mixed chimerism MC and or secondary graft failure SGF in hematopoietic stem cell transplantation for aplastic anemia was retrospectively evaluated. SGF with both MC recipient and donor type chimerism was observed. Patients who developed SGF with both types of chimerism had unfavorable outcomes. The use of fludarabine may affect the occurrence of SGF with both types of chimerism. |
S1083879119306615 | Patients undergoing allogeneic stem cell transplantation usually require nutritional support . There is no consensus on whether enteral support through tube feeding should be preferred . A recent randomized study could not detect any difference between enteral and parenteral feeding with regard to post transplant outcomes whereas 2 retrospective studies described an association between enteral feeding and a favorable post transplant outcome . We compared pre and post transplant plasma metabolomic profiles for 10 patients receiving mainly enteral nutritional support and 10 patients receiving mainly parenteral support . Samples were collected before conditioning and 3 weeks post transplant 824 metabolites were analyzed using mass spectrometry . The pretransplant metabolite profiles showed a significant overlap between the 2 groups . Post transplant samples for both patient groups showed an increase of secondary bile acids and endocannabinoids whereas reduced levels were seen for food preservatives plasmalogens and retinol metabolites . The main post transplant differences between the groups were decreased levels of fatty acids and markers of mitochondrial activation in the control group indicating that these patients had insufficient energy intake . A significant effect was also seen for heme bilirubin metabolism for the parenteral support . To conclude allotransplant recipients showed altered metabolic profiles early after transplantation this was mainly due to the conditioning transplantation reconstitution whereas the type of nutritional support had minor effects . | The type of nutritional support seems to have relatively minor effects on the post transplant metabolomic profile. The metabolic profile of patients treated with standard care nutritional support indicates an insufficient calorie intake compared with patients treated with individualized enteral nutritional support. |
S1083879119306627 | Hematopoietic stem cell transplantation recipients are vulnerable to invasive pneumococcal disease with reported IPD rates ranging from 3.81 to 22.5 1000 HSCT . This IPD risk could relate to immunodeficiency low vaccination uptake and poor immunogenicity of pneumococcal polysaccharide vaccine . Literature comparing the clinical effectiveness of pneumococcal conjugate vaccination and PPV after HSCT is limited . In this retrospective analysis of HSCT recipients at our center from 2004 to 2015 we evaluated vaccination uptake and compared IPD rates in patients receiving PPV and PCV . IPD was determined from microbiological results for all HSCT recipients from January 2004 to June 30 2019 . Eight hundred patients had a total of 842 HSCT events including autologous HSCT and allogeneic HSCT . More than 90 of the HSCT recipients were enrolled and 93 of surviving HSCT recipients completed the vaccination protocol . Fifteen IPD episodes occurred in 13 patients between 2004 and June 30 2019 . Thirteen episodes occurred in the pre 2010 group even though 9 of 13 serotyped isolates were covered by PPV . Two episodes occurred in the post 2010 group neither serotype was covered by PCV . Thus with PCV introduction IPD rate was significantly reduced from 38.5 1000 unique HSCTs pre 2010 to 4.0 1000 unique HSCTs post 2010 | Hematopoietic stem cell transplantation HSCT recipients have high rates of invasive pneumococcal disease IPD . Patients with multiple myeloma are at particularly higher risk of IPD following HSCT. Compared with pneumococcal polysaccharide vaccine pneumococcal conjugate vaccine significantly reduced IPD in HSCT recipients. A nurse led vaccination program produced high vaccination completion rates. |
S1083879119306639 | Allogeneic hematopoietic stem cell transplantation is widely performed in children and adolescents with hematologic diseases including very high risk leukemia . With increasing success and survival rates the long term sequelae of HSCT have become important . Here we provide guidance to the prevention and treatment of the most common bone morbiditiesosteoporosis and osteonecrosisemerging in the context of HSCT in children and adolescents . We give an overview on definitions symptoms and diagnostics and propose an algorithm for clinical practice based on discussions within the International Berlin Frankfurt Mnster Stem Cell Transplantation Committee and the Pediatric Disease Working Party of the European Society for Blood and Marrow Transplantation our expert knowledge and a literature review . | Bone mass deficits in children with leukemia following hematopoietic stem cell transplantation HSCT are multifactorial. Attention is needed for children with less potential to recover from low bone mineral density. Risk factors for osteonecrosis ON include older age at HSCT steroids chronic graft versus host disease and prior ON. Management of ON in children with acute lymphoblastic leukemia following HSCT remains challenging. |
S1083879119306652 | Despite the fact that the choice of donors and the number of sources of hematopoietic stem cells have increased a sibling remains a preferred donor for allogeneic hematopoietic stem cell transplantation . Transplant donation between siblings is a unique life experience that may have an impact on their future relationship . The aim of the study was to quantitatively measure the quality of life in patients who underwent transplant and to describe the relationship between a recipient and a sibling donor after HSCT . We identified and invited 82 adults aged 18.0 to 38.7 years who underwent HSCT in our center and their sibling donors to participate in this survey . Forty five patients and their siblings consented to take part in the study . The studied group consisted of 45 matched siblings donor HSCT recipients aged 18.0 to 36.2 years who underwent MSD HSCT at the age of 5.8 to 16.3 years and their sibling donors aged 21.0 to 36.0 years who were aged 11.2 to 20.2 years at bone marrow harvesting . For QoL and sibling relationship assessment we used the Functional Assessment of Cancer TherapyBone Marrow Transplantation and the Adult Sibling Relationship Questionnaire . Higher scores indicate better quality of life in each scale of the FACT BMT and the more significant is the factor in a sibling relationship measured by the ASQR . The questionnaires were given to both subgroups HSCT recipients and donors and the results were compared with each other . The overall result of the FACT BMT questionnaire was 117 35.0 . The highest QoL was found in the functional and social well being subscales whereas the worst was in the emotional well being subscale . Statistically the QoL score was not influenced by current age | Quality of life in adult patients after hematopoietic stem cell transplantation in childhood was good. Sibling donor recipient relationship is unbalanced with higher level of rivalry presented among donors. Further multicenter studies are necessary to assess all aspects of sibling relationship years after transplantation experience and finally to provide effective psychological interventions for an often overlooked population of pediatric sibling donors. |
S1083879119306688 | Vitamin D deficiency is a well described phenomenon in pediatric patients undergoing hematopoietic stem cell transplant . VD modulates inflammation and deficiency pre HSCT and at day 100 has been associated with graft versus host disease and poorer survival . However a paucity of data has specifically described the association between VD status and immune mediated complications including GVHD and veno occlusive disease . Additionally data to guide recommendations for VD monitoring and supplementation during HSCT are scarce . Our primary objective was to evaluate the association between VD and post HSCT complications . The key secondary aim was to evaluate the routine use and efficacy of VD monitoring and supplementation practices . To our knowledge this is the largest study of its kind in the pediatric population . This retrospective study evaluated VD level before and 1 year after HSCT VD supplementation practices and their association with acute GVHD VOD and survival in pediatric patients who received autologous and allogeneic HSCT for both malignant and nonmalignant diseases from January 2013 to April 2018 . Of 314 HSCTs 43 of patients had VDL measured before HSCT 61 of this cohort had pre HSCT VD insufficiency . Neither pre HSCT nor follow up VDL was associated with the incidence of GVHD or VOD . Supplementation did not result in significantly different post HSCT VDL.VDL was correlated with overall survival every 10 ng mL increase in VDL was associated with a 28 decreased risk of death | Pediatric patients receiving HSCT have high risk of vitamin D insufficiency 61 . Substantial variation exists in vitamin D monitoring and supplementation practices. Pre HSCT vitamin D levels were not associated with incidence of GVHD or VOD. Higher vitamin D levels were associated with decreased risk for all cause mortality. |
S108387911930669X | There are more than 30 million potential unrelated hematopoietic progenitor cell donors listed on international registries but 30 to 50 are unavailable after matching a patient . In the United States racial ethnic minorities opt out of donation at higher rates and a previous study identified factors associated both with attrition and ethnic group membership . Attrition among minorities is also higher in the Anthony Nolan UK registry and 56 in nonwhite British but it is not clear what factors produce higher attrition in the United Kingdom and whether they are similar to those found in the United States . Three hundred fifty seven UK potential donors who matched a patient completed a questionnaire . Key factors were compared by donation decision and by race ethnicity . The pattern of UK results was compared with that of the previous US study for variables assessed in both studies . Across WB and NWB donors higher attrition was associated with poorer physical mental health greater ambivalence and more concerns about donation . Donors who opted out also reported less interaction with the registry and 16 indicated that more interaction with the registry would have changed their decision . Those opting out of the registry and minorities were both more likely to report religious objections to donation and to mistrust the fairness of HPC allocation . The pattern of findings was similar in UK and US samples . Registries should maintain contact with potential donors after recruitment aiming to educate members about the donation procedure and to address potential misconceptions associated with religious beliefs and HPC allocation . | Potential HPC donors who opted out were more ambivalent and had more concerns. Potential HPC donors who opted out reported less interaction with the registry. Sixteen percent said more interaction with the registry would have changed their decision. Minorities reported more religious objections and mistrust about HPC allocation. Patterns of results were similar for UK and US based registries. |
S1083879119306706 | The utility of surveillance imaging after autologous hematopoietic cell transplantation in relapsed refractory diffuse large B cell lymphoma remains unclear . The purpose of this study was to determine whether surveillance imaging predicts survival after AHCT . At the University of Minnesota serial imaging for early relapse detection has been used prospectively for all consecutive AHCT recipients treated since 2010 . The present analysis included 91 AHCT recipients with DLBCL who underwent | Routine PET imaging at day 100 post autologous HCT detects asymptomatic relapse in about 30 of patients with DLBCL and portents worse survival. High SUV. at day 100 PET is associated with survival of less than 1 year post transplant. Identifying this high risk cohort in autologous HCT recipients highlights the opportunity to develop preemptive interventions to improve survival in DLBCL. |
S1083879119306718 | In this prospective randomized study we compared the outcomes of single unit umbilical cord blood transplantation and unmanipulated haploidentical stem cell transplantation with post transplantation cyclophosphamide in adults with hematologic malignancies . All patients received a myeloablative conditioning regimen consisting of thiotepa busulfan and fludarabine with antithymocyte globulin added for UCBT recipients . Nineteen patients were randomized to UCBT and the other 26 to haplo HSCT . Four patients allocated to the haplo HSCT arm lacked a suitable donor and were crossed over to the UCBT arm . Finally 23 underwent UCBT and 22 underwent haplo HSCT . The cumulative incidence of neutrophil recovery was 87 at a median of 19 days in the UCBT arm versus 100 at a median of 17 days in the haplo SCT arm | Myeloablative haploidentical stem cell transplantation with post transplantation cyclophosphamide provides improved outcomes compared with antithymocyte globulin containing single unit umbilical cord blood transplantation. Some 15 of patients lacked an appropriate haploidentical donor. |
S108387911930672X | Allogeneic hematopoietic stem cell transplantation remains the only potentially curative option for myelodysplastic syndromes but is severely limited by nonrelapse mortality especially in this mostly older population . Comorbidity assessment is crucial to predict NRM and often assessed with the Hematopoietic Cell Transplantation Specific Comorbidity Index . Moreover the impact of age on NRM still remains a matter of debate . In recent years the age at which transplants are made has been progressively increasing and patients with comorbidities have become more common . Extricating the respective roles of age and comorbidities in toxic mortality is all the more important . This study by the European Group for Blood and Marrow Transplantation registry included 1245 adult patients who underwent a first allogeneic stem cell transplantation for MDSs between 2003 and 2014 . Overall 4 year NRM and overall survival were 32 and 47 respectively . When considered as continuous predictors HCT CI score and age were associated with an increased hazard ratio for NRM . In multivariate analysis age band HR 1.13 95 CI 1.02 to 1.25 | Allotransplant for myelodysplastic syndrome is limited by high nonrelapse mortality. Comorbidities assessed by the original Sorror score impact mortality negatively. Chronological age also continues to play an independent prognostic role on mortality. Both age and comorbidities should be integrated in the allotransplant decision process. |
S1083879119306731 | Killer immunoglobulin like receptor and KIR ligand interactions play an important role in natural killer cell mediated graft versus leukemia effect following hematopoietic cell transplantation . However there is considerable heterogeneity in the KIR gene and KIRL content in individuals making it difficult to estimate the full clinical impact of NK cell reconstitution following HCT . Here we present a novel adaptive mathematical model designed to quantify these interactions to better assess the influence of NK cell mediated alloreactivity on transplant outcomes . Ninety eight HLA matched unrelated donor HCT recipients were studied retrospectively . The KIR KIRL interactions were quantified using a system of matrix equations . Unit values were ascribed to each KIR KIRL interaction and the directionality of interactions was denoted by either a positive or negative symbol these interactions were then summed . The absolute values of both the missing KIRL and inhibitory KIR KIRL interactions were significantly associated with overall survival and relapse . These score components were initially used to develop a weighted score and subsequently a simplified nonweighted KIR KIRL interaction score . Increased w KIR score and IM KIR score were predictive of all cause mortality and relapse .37 | An adaptive mathematical model has been developed to quantify killer immunoglobulin like receptor KIR KIR ligand KIRL interactions. The magnitude of inhibitory and missing KIR KIRL interactions predicts overall survival and relapse risk following HLA matched unrelated donor URD hematopoietic cell transplantation HCT . Cumulative known KIR KIRL interactions predict clinical outcomes after URD HCT. High inhibitory KIR KIRL interaction scores correlates with robust natural killer cell recovery after URD HCT. |
S1083879119306755 | Hematopoietic stem cell transplantation has been used to treat many malignant and nonmalignant hematologic conditions however the use of HSCT in patients who refuse blood transfusions has rarely been described in the literature and no data have been published concerning haploidentical HSCT without the use of blood products . The aim of this study is to describe the experience of a Brazilian group in performing 21 HSCTs without the use of blood components in the first 100 days after transplantation which is the period corresponding to the greatest risk of toxicity for this procedure . We developed 21 HSCTs without transfusion support in 19 patients admitted to 2 Brazilian transplantation centers . The patients were subjected to stem cell mobilization and different conditioning regimens . No mortality related to the procedure occurred among the transplant recipients . The global survival rate after 100 days which is the period related to the immediate toxicity of HSCT was 94.7 and the median duration of follow up was 980 days with an overall survival rate of 68.4 . Thus refusal of blood transfusion is not an absolute contraindication for HSCT . This therapy is feasible in specific situations when the patient clearly expresses a desire to avoid blood transfusions and when favorable clinical conditions are achievable with strict specialized medical monitoring . | Bloodless bone marrow transplantations were performed without treatment related mortality. There are no previously published data on haploidentical transplantation without blood products. Transplantation without transfusion can be used in other conditions without hemotherapy support. |
S1083879119306767 | Chronic graft versus host disease is a heterogenous syndrome whose symptoms and treatment are often associated with decreases in functional status and quality of life among survivors of transplantation . We explored definitions of cGVHD related disability and factors associated with disability in cGVHD . We analyzed 371 patients with cGVHD requiring a new systemic therapy with enrollment and 18 month assessments through the Chronic GVHD Consortium evaluating disability as a composite endpoint including any 1 of 5 impairments previously defined by Fatobene et al . We also evaluated disability defined as an 8 point decline in a human activity profile score or a 20 decline in Karnofsky Performance Status from enrollment to 18 months . At enrollment 47 of patients had at least 1 of the 5 Flowers disability features with 50 of this group acquiring additional impairments at 18 months . Of the 197 patients with no Flowers disability at enrollment 50 progressed with disability features at 18 months . We found that any progressive Flowers impairment was associated with a decline in HAP KPS as well as with increased National Institutes of Health severity scores at 18 months . Enrollment mouth scores and patient reported eye and skin scores were significantly associated with progressive impairment at 18 months . Progressive disability at 18 months did not predict subsequent nonrelapse mortality . Additional studies to define chronic GVHD related disability and risk factors are needed to develop this important patient centered outcome . | Disability as defined by progressive chronic graft versus host disease GVHD impairments are associated with decline in human activity profile scores and performance status at 18 months. Worse oral scores and patient reported eye and skin scores are significantly associated with progressive chronic GVHD impairment at 18 months. |
S1083879119307049 | Methotrexate in combination with a calcineurin inhibitor has been commonly used for prophylaxis of graft versus host disease following umbilical cord blood transplantation in Japan . However the appropriate prophylactic MTX dosage in UCBT has not been established to date . To determine the preferential GVHD prophylaxis in UCBT this study retrospectively investigated the administration of short term MTX for 2 days versus 3 days . Of 103 adult patients submitted to UCBT enrolled in the study 73 received tacrolimus with 2 days of MTX given at 10mg m | In this comparative analysis of 2 day and 3 day methotrexate MTX administration in umbilical cord blood transplantation UCBT. the very short term vs MTX tacrolimus TAC group had earlier neutrophil engraftment compared with the short term MTX TAC group. In a high risk population vsMTX TAC was associated with lower relapse incidence. |
S1083879119307050 | Acute graft versus host disease is a major complication following hematopoietic cell transplantations . We have shown that HCT recipients in whom either the donor or patient had inherited chromosomally integrated human herpesvirus 6 have a higher incidence of developing more severe aGVHD . Previous studies established that increased proinflammatory cytokines are associated with increased risk for aGVHD and nonrelapse mortality post HCT . We hypothesized that HCT recipients with donor or recipient iciHHV 6 iciHHV 6 | Hematopoietic cell transplantation HCT recipients in whom the donor or recipient had inherited chromosomally integrated human herpesvirus 6 iciHHV 6. have higher plasma C reactive protein and TNFRp55 cytokine concentrations. IciHHV 6. HCT recipients had earlier onset graft versus host disease by a median of 7 days. There were no differences in cytokine levels among healthy donors with or without iciHHV 6. |
S1083879119307062 | fludarabine with intravenous busulfan at doses of 3.2 mg kg or 6.4 mg kg . Hepatic veno occlusive disease sinusoidal obstruction syndrome is a serious complication of hematopoietic stem cell transplantation that is felt to be triggered at least in part by damage to the liver sinusoidal endothelium from cytotoxic conditioning regimens . Accordingly the incidence of VOD SOS after reduced intensity conditioning HCT is low compared with myeloablative transplantation and the natural history risk factors and outcomes of VOD SOS after RIC have not been well characterized . We retrospectively reviewed 1583 consecutive patients receiving RIC HCT at the Dana Farber Cancer Institute between 2007 and 2017 and ascertained 26 cases of VOD SOS . The median day of VOD SOS onset was 26 days and the cumulative incidence at day 50 was 1.6 1.1 to 2.4 . Day 100 nonrelapse mortality rate was 23 in the VOD SOS cohort compared with 6.4 in patients without VOD SOS | Veno occlusive disease sinusoidal obstruction syndrome VOD SOS is rare after reduced intensity conditioning RIC transplantation with a cumulative incidence of 1.6 in our large modern cohort. VOD SOS continues to be associated with a high nonrelapse mortality NRM in our cohort day 100 NRM was 23 in patients with VOD SOS compared with 6.4 in patients without VOD SOS. VOD SOS in RIC patients often does not meet classical Baltimore Seattle criteria and has a later onset a lower peak bilirubin and better survival than VOD SOS in patients with myeloablative conditioning. VOD SOS after RIC is strongly associated with higher dose busulfan 6.4 versus 3.2 mg kg in the RIC regimen and use of sirolimus in the graft versus host disease prophylaxis regimen. |
S1083879119307074 | Azithromycin exposure during the early phase of allogeneic hematopoietic cell transplantation has been associated with an increased incidence of hematologic relapse . We assessed the impact of azithromycin exposure on the occurrence of relapse or new subsequent neoplasm in patients with bronchiolitis obliterans syndrome after HCT who are commonly treated with azithromycin alone or in combination with other agents . In a retrospective study of patients with BOS from 2 large allograft centers the effect of azithromycin exposure on the risk of relapse or SN was estimated from a Cox model with a time dependent variable for treatment initiation . The Cox model was adjusted on time fixed covariates measured at cohort entry selected for their potential prognostic value . Similar models were used to assess the exposure effect on the cause specific hazard of relapse SN and death free of those events . Sensitivity analyses were performed using propensity score matching . Among 316 patients 227 were exposed to azithromycin after BOS diagnosis . The corresponding adjusted hazard ratio in patients exposed to azithromycin versus unexposed was 1.51 0.90 to 2.55 for relapse or SN 0.82 for relapse and 2.00 for SN . Patients exposed to azithromycin had a significantly lower cause specific hazard of death free of neoplasm and relapse . In conclusion exposure to azithromycin after BOS after HCT was associated with an increased risk of SN but not relapse . | Azithromycin is associated with increased second cancers in bronchiolitis obliterans. Azithromycin is not associated with increased relapse in bronchiolitis obliterans. There is a decreased cause specific hazard of death free of malignancy with azithromycin exposure. |
S1083879119307086 | Although thymus independent donor derived T cell expansion may determine the occurrence of graft versus host disease and relapse after transplantation the characteristics and dynamics of the expansion process remain unclear . To address this issue we monitored T cell receptor repertoire at day 0 day 28 and day 61 after transplantation in 30 patients with hematologic malignancies by next generation sequencing . The clonality index showed an increasing clonality over time | Homeostatic peripheral expansion predominates in the first month after allogeneic hematopoietic stem cell transplantation. Antigen driven expansion in the second month leads to a graft versus tumor GvT effect. TCRI200bc 1.0 indicates a potent GvT effect and freedom from relapse within a year. The GvT associated clones share some V and J segments among nonrelapse patients. |
S1083879119307098 | Outbreaks of viral infections such as measles are regularly observed and pose a serious threat to recipients of allogeneic hematopoietic cell transplantation . The questions of how long cellular and humoral protective host immunity persists and whether donor immunity can be transferred has not been clarified . Here we present a retrospective analysis of humoral immunityserial antibody titers against measles mumps and rubellain 331 patients who underwent allogeneic HCT at our single center between 2002 and 2015 . Associations between the loss of protective antibody levels and clinical patient characteristics and transplantation parameters were examined . In general antibody protection against measles persisted longer with 72 of patients maintaining sufficient titers at 5 years post HCT even without revaccination while at that time only 65 and 50 of patients had protective immunity against rubella and mumps respectively . The great majority of donors were seropositive for all 3 viruses however it appeared that donor humoral immunity could not be transferred and had no impact on post HCT serostatus . Rather the most relevant factor for persistent protective antibody titers against measles and rubella was whether patients were born before the introduction of the respective vaccine and thus were immunized by the wild type disease inducing virus instead of the vaccine . Moreover the presence of moderate and severe chronic graft versus host disease was associated with more rapid loss of immune protection . In contrast underlying disease intensity of the conditioning regimen use of antithymocyte globulin age and graft source had no influence on antibody titers . Overall our findings suggest that the majority of antibodies against measles mumps and rubella originate from residual host cells whereas donor immune status appears to have no influence on antibody protection post HCT . | Loss of protective antibody levels over time differed substantially between measles mumps and rubella in patients following allogeneic hematopoietic cell transplantation HCT . Protective immunity against measles and rubella that was acquired by wild type viral infection persisted longer than immunity due to vaccination. Intensity of the conditioning regimen and the use of antithymocyte globulin had no influence on the decline of antibody titers against measles mumps and rubella post HCT. The presence of chronic graft versus host disease was associated with a more rapid loss of protective immunity against measles post HCT. |
S1083879119307104 | Acute graft versus host disease contributes to poor outcomes following allogeneic hematopoietic cell transplantation . Data are limited regarding the economic burden of acute GVHD particularly steroid refractory or high risk disease . This retrospective analysis of the Premier Healthcare Database reports inpatient healthcare resource utilization costs and mortality during initial hospitalization for allogeneic HCT and through 100 days post HCT among patients who developed acute GVHD including a subgroup with SR HR disease compared with patients without GVHD . The analysis included adults discharged for first HCT between January 1 2011 and June 30 2016 . During the initial hospitalization for HCT patients with acute GVHD and SR HR acute GVHD had significantly longer median lengths of stay and higher median total costs versus patients with no GVHD n 1529 | Inpatient healthcare resource utilization HCRU and costs for acute versus no graft versus host disease GVHD up to 100 days post hematopoietic cell transplantation HCT were assessed. Acute GVHD was associated with greater inpatient HCRU and total costs compared with no GVHD. Inpatient HCRU and costs were especially high with steroid refractory acute GVHD. Acute GVHD was associated with high 100 day post HCT inpatient mortality. |
S1083879119307116 | Allogeneic stem cell transplant is considered in diffuse large B cell lymphoma patients with chemorefractory disease or who have relapsed after autologous SCT . Here we present the first report of alloSCT using the R BEAM conditioning regimen in DLBCL patients . | Allogeneic transplant is a viable treatment in diffuse large B cell lymphoma. The R BEAM regimen is associated with significantly higher grades III to IV acute GVHD. Nonrelapse mortality is substantial. A few patients attain a durable response indicating a graft versus lymphoma effect. |
S108387911930713X | Basiliximab has been used successfully as a second line treatment for steroid refractory acute graft versus host disease in adult patients after haploidentical hematopoietic stem cell transplant but has not been studied separately in the pediatric setting . We retrospectively reviewed 100 pediatric patients after haplo HSCT receiving basiliximab for grades II III and IV SR aGVHD between January 2015 and December 2017 . The median number of basiliximab doses was 4 . The day 28 overall response rate was 85 with complete response in 74 of patients partial response in 11 of patients and no response in 15 of patients . The day 28 overall response rates were 94.6 in skin SR aGVHD 81.6 in gut SR aGVHD and 66.7 in liver SR aGVHD . Infectious complications included bacterial infection presumed or documented fungal infections cytomegalovirus viremia Epstein Barr virus viremia human herpesvirus 6 viremia and herpes simplex virus viremia . The 3 year overall survival disease free survival nonrelapse mortality and relapse rates between responders and nonresponders were 81.3 versus 46.7 | This study represents the first report on the outcomes of basiliximab as a treatment for steroid refractory SR acute graft versus host disease aGVHD in pediatric patients after allo HSCT. The overall response rate of basiliximab was 85 including complete response in 74 and partial response in 11 . No life ending complications could be attributed solely to basiliximab. |
S1083879119307141 | Natural killer cells expressing killer cell immunoglobulin like receptors can recognize specific HLA class I molecules as their ligands . By studying a large Japanese transplant registry we compared transplant outcomes between patients heterozygous for HLA C | Absence of KIR2DL1 ligands increases relapse in HLA matched hematopoietic stem cell transplantation HSCT for acute lymphoblastic leukemia ALL . This trend is prominent in patients with Ph negative ALL who experienced acute graft versus host disease. The trend is the opposite of that in our previous report analyzing HSCT for acute myeloid leukemia chronic myeloid leukemia. |
S1083879119307414 | The impact of allele level HLA mismatch on outcomes of cord blood transplantation has not been well established . We retrospectively analyzed the effects of HLA allele matching at HLA A B C and DRB1 in cord blood transplantation for acute myeloid leukemia acute lymphoblastic leukemia and myelodysplastic syndrome . In multivariate analysis overall survival significantly deteriorated in the 4 allele or higher mismatch in pediatric cases and 2.85 for 3 1 8 match and the 5 allele or higher mismatch in adult cases . Incidence of grade to acute graft versus host disease was low in the 8 8 match and 1 allele mismatch in pediatric cases and the 8 8 match in adult cases . On the other hand a higher incidence of relapse was noted in the 8 8 match in adults . The incidence of neutrophil and platelet engraftment decreased in the 3 allele or higher mismatch in adults . In subgroup analysis of graft versus host disease prophylaxis in adult cases a deteriorating effect on OS of HLA 5 allele or higher mismatch was more significant in cases with calcineurin inhibitor with methotrexate than with mycophenolate mofetil . These results suggest that allele level HLA mismatch affects the outcomes of cord blood transplantation . Information on HLA allele matching at HLA A B C and DRB1 may be useful for cord blood unit selection . | HLA A B C and DRB1 allele mismatch effects were examined in 4050 cases of cord blood transplants. Overall survival OS deteriorated in HLA 5 allele and higher mismatch in adult cord blood transplantation CBT . OS deteriorated in HLA 4 allele and higher mismatch in pediatric CBT. In adult cases 8 8 match mitigated severe acute graft versus host disease GVHD but increased the relapse rate. In pediatric cases 8 8 match and 1 allele mismatch mitigated acute GVHD. |
S1083879119307426 | Torque teno virus is a nonenveloped single stranded circular DNA virus of the family of Anelloviridae . The first contact with TTV usually occurs in early childhood followed by persistent infection in bone marrow and lymphocytes . Increased levels of TTV DNA are found in the serum in various states of immune deficiency . The objective of this study was to assess if monitoring of TTV viremia after allogeneic hematopoietic stem cell transplantation is a predictive marker for immune related clinical complications . In a retrospective study 2054 whole blood samples from 123 patients were tested for viral loads of TTV DNA by real time PCR within 345 days after allo HSCT . We enrolled all patients who underwent allo HSCT between September 2015 and April 2018 . Clinical and laboratory data were collected and statistically analyzed . Patients with an underlying lymphatic malignancy had significantly higher torque teno viral loads compared with patients with an underlying malignant myeloid disease | A multifactorial influence determines the level and kinetics of torque teno TT viral load. Numerous new influencing factors were identified. Significant differences were only visible after day 50 after allogeneic hematopoietic stem cell transplantation. Clinically relevant events showed no significant impact on TT viral load. An early prognostic statement regarding the further clinical outcome is limited. |
S1083879119307438 | Follow up is integral for hematopoietic cell transplantation care to ensure surveillance and intervention for complications . We characterized the incidence of and predictors for being lost to follow up . Two year survivors of first allogeneic HCT or autologous HCT for malignant nonmalignant disorders between 2002 and 2013 reported to the Center for International Blood and Marrow Transplant Research were selected . The cumulative incidence of being lost to follow up was calculated . Marginal Cox models were fit to evaluate predictors . The 10 year cumulative incidence of being lost to follow up was 13 12 to 14 in adult allogeneic HCT survivors 15 in adult autologous HCT survivors 25 in pediatric allogeneic HCT survivors and 24 in pediatric autologous HCT survivors . Factors associated with being lost to follow up include younger age nonmalignant disease public no insurance residence farther from the tranplantation center and being unmarried in adult allogeneic HCT survivors older age and testicular germ cell tumor in adult autologous HCT survivors older age public no insurance and nonmalignant disease in pediatric allogeneic HCT survivors and older age in pediatric autologous HCT survivors . Follow up focusing on minimizing attrition in high risk groups is needed to ensure surveillance for late effects . | Follow up is an integral part of hematopoietic cell transplantation HCT care. We characterized the incidence of and predictors for being lost to follow up. The proportion of HCT survivors lost to follow up is concerning. Subgroups of HCT survivors remain at higher risk of being lost to follow up. Follow up efforts focusing on minimizing attrition in high risk groups is needed. |
S108387911930744X | The significant advancements made in the field of allogeneic hematopoietic stem cell transplantation have ensured increased longevity in transplant recipients . However they do have late effects that may adversely affect the endocrine system bone health and body composition . This study was undertaken to evaluate bone mineral density trabecular bone score and body composition in recipients of allo HSCT and compare them with age sex and body mass index matched controls . This was a cross sectional study done in 63 cases and 65 matched controls . The mean femoral neck BMD was found to be lower in cases than in controls versus 0.846 g cm | The mean femoral neck bone mineral density BMD was lower in recipients of allogeneic hematopoietic stem cell transplantation. Myeloablative conditioning had an adverse effect on BMD at the femoral neck. Lumbar spine BMD was lower in the group that received total body irradiation. The prevalence of sarcopenia was significantly higher in cases than in controls. Calcium and vitamin D supplements are recommended in these patients. Consider graded strength training exercises to build muscle mass. |
S1083879119307451 | Cytomegalovirus results in significant morbidity and mortality following hematopoietic cell transplantation . Establishing the cost and clinical impact is imperative to the selection of appropriate CMV preventative strategies . This is a retrospective cohort study of consecutive patients undergoing their first allogeneic HCT between January 1 2009 and December 31 2013 . Detailed clinical and institutional cost data were obtained from the start of conditioning through 1 year post transplantation . Baseline characteristics resource utilization costs and outcomes were compared between patients with and without clinically significant CMV infection . One hundred seventy out of 388 patients developed csCMVi within 1 year after HCT . Within the first year post HCT patients with csCMVi had a significantly longer transplantation related length of stay mean 91.7 days versus 78.3 days | Cytomegalovirus following transplantation carries significant morbidity and mortality. Implementation of efficacious preventative strategies is imperative. Strategy selection requires an assessment of the economic impact of cytomegalovirus. |
S1083879119307475 | Radioimmunotherapy has the potential to reduce the incidence of relapse after allogeneic hematopoietic cell transplantation in patients with advanced stage multiple myeloma . In this study we evaluated the efficacy of RIT in combination with chemotherapy based reduced intensity conditioning . RIT was based on the coupling of an anti CD66 antibody to the beta emitter 188 rhenium for targeted bone marrow irradiation . Between 2012 and 2018 30 patients with MM most of them heavily pretreated with various therapies including proteasome inhibitors immunomodulatory drugs anti CD38 antibodies and autologous hematopoietic cell transplantation were treated with a RIT RIC combination before allo HCT . In addition to a fludarabine plus melphalan or treosulfan based RIC a median dose of 18.1 Gy 14.6 to 24.1 Gy was applied to the bone marrow . After a median duration of follow up for surviving patients of 2.1 years the 2 year progression free survival and overall survival rates were 43 26 to 73 and 55 respectively . The 2 year nonrelapse mortality and cumulative incidence of progression were 17 and 46 respectively . Renal toxicity and mucositis were the most frequent extramedullary side effects . In conclusion the addition of RIT to RIC was safe and feasible and resulted in promising outcomes compared with those previously reported for RIC based allo HCT without the addition of RIT in patients with relapsed refractory MM . Nevertheless despite the addition of RIT relapse after allo HCT remained a major determinant of therapeutic failure . Therefore the development of novel RIT strategies is needed . | Radioimmunotherapy RIT is a novel concept for conditioning in patients with multiple myeloma MM . CD66 directed RIT was combined with reduced intensity conditioning RIC . The CD66 RIT RIC strategy is safe and feasible for patients with MM. The combined therapy results in promising outcomes after allogeneic hematopoietic cell transplantation in patients with MM. |
S1083879119307487 | Allogeneic blood or marrow transplantation remains the only treatment for chronic lymphocytic leukemia with curative potential . Although post transplantation cyclophosphamide reduces allo BMT toxicity by decreasing the risk of graft versus host disease its effect on CLL allo BMT outcomes is unknown . We studied 64 consecutive patients with CLL who underwent nonmyeloablative haploidentical allo BMT at Johns Hopkins Sidney Kimmel Comprehensive Cancer Center . In this cohort the 4 year overall survival was 52 40 to 68 and progression free survival was 37 . Six patients experienced engraftment failure . PTCy prophylaxis was associated with a modest cumulative incidence of 1 year grade II IV acute GVHD and 2 year chronic GVHD . We demonstrate that NMA haploidentical allo BMT with PTCy is a safe and effective treatment option . | Outcomes of haploidentical allogeneic bone marrow transplantation allo BMT may be similar to those reported for matched donor allo BMT in patients with chronic lymphocytic leukemia CLL . Post transplantation cyclophosphamide prophylaxis is associated with low rates of acute and chronic graft versus host disease. Pre allo BMT bone marrow CLL involvement 20 hinders engraftment. Unfavorable risk CLL prognostic features should not preclude the consideration of allo BMT. |
S1083879119307505 | There have been sporadic reports of the development of delayed disease recurrence after bone marrow transplantation for severe aplastic anemia despite sustained majority or full donor chimerism . This is termed donor type aplasia . We describe the management and outcome of 11 pediatric patients from 8 institutions in Europe the United States and the Middle East who developed DTA at a mean of 35 months post transplant . These patients were initially transplanted at a mean age of 10.0 years 9 from matched sibling donors and 2 from matched unrelated donors . Attempts to treat DTA with varying combinations of additional immunosuppression failed . Ten patients have received a conditioned second transplant 9 from the same donor and 1 from a new matched unrelated donor . Aplasia has resolved in the remaining patient in response to ongoing eltrombopag therapy . All patients were alive at a mean of 92 months after a second transplant 6 are in complete remission but 4 suffered from second recurrent DTA at 16 to 129 months after retransplant and required further transplant therapy . | DTA is recurrent pancytopenia despite sustained majority donor chimerism after BMT for SAA. Treatment with immunosuppressive therapy or stem cell boosts has not been effective. Most patients required retransplantation from the same or an alternative donor. Sibling retransplantation has sometimes been followed by further relapse after many years. Eltrombopag may be of benefit in some patients. |
S1083879119307797 | We compared the incidence of refractory thrombocytopenia and platelet transfusion requirements in 35 children who developed veno occlusive disease with 35 matched control subjects who underwent hematopoietic stem cell transplant but did not develop VOD . RT developed in 100 of the VOD patients at a median of 8 days before VOD diagnosis as compared with 71.5 of the control group . VOD patients required more platelet transfusions than control subjects versus 3.57 mL kg respectively with a statistically significant difference | Refractory thrombocytopenia is a valid and early diagnostic criteria for VOD in children as included in the 2017 EBMT criteria. RT occurs in 100 of the patients with VOD at a median of 8 days before VOD diagnosis. Platelet transfusion requirements in VOD patients is higher than in the patients who do not develop VOD. The positive predictive value of developing VOD was 89 in patients needing 7 mL kg day of platelets. |
S1083879119307815 | Hematopoietic stem cell transplantation is a primary treatment for various inherited metabolic disorders . Achieving stable and sustained engraftment while minimizing transplantation related morbidity and mortality is critical to optimizing outcomes for IMDs . Traditional regimens have used myeloablative approaches primarily busulfan and cyclophosphamide which is associated with significant regimen related toxicity . Alternatively reduced toxicity regimens such as busulfan and fludarabine have been proposed to offer similar efficacy with reduced toxicities . We compared transplantation related outcomes with BuCy based and BuFlu based conditioning in patients with IMDs . We retrospectively analyzed the University of Minnesota s transplantation database for patients with IMDs who underwent HCT using a BuCy or BuFlu preparative regimen between March 2008 and September 2017 . Overall survival event free survival and incidence of neutrophil and platelet recovery were determined using standard definitions . Complications such as graft failure sinusoidal obstruction syndrome hemorrhagic cystitis and respiratory failure were compared . Graft failure includes primary and secondary aplastic graft failure with and without autologous recovery . The incidence of viral infections post transplantation in the 2 regimens was also determined . A total of 99 patients underwent HCT for IMDs during the study period . Sixty four patients received BuCy conditioning and the other 35 received BuFlu . Hurler syndrome and adrenoleukodystrophy were the most common IMDs and umbilical cord blood was the most common graft source . One year OS was similar in the 2 groups 81.2 in BuCy versus 85.5 in BuFlu | BuCy based conditioning is associated with greater regimen related toxicity but earlier CD3 donor engraftment. BuFlu based conditioning is associated with lower toxicity but higher rates of graft failure and immune cytopenias. Newer approaches and modification of conditioning regimen are needed to optimize benefits. |
S1083879119307827 | Anti thymocyte globulin is an established approach to decrease chronic GVHD yet the exact mechanism is uncertain . To better understand the mechanism of action of ATG in preventing cGVHD we evaluated the day 100 immune reconstitution of known cGVHD cellular biomarkers using patients from the randomized Canadian Bone Marrow Transplant Group 0801 trial which demonstrated a significant impact of ATG on cGVHD . In a separate companion biology study we evaluated the impact of ATG prophylaxis on cGVHD cellular markers at day 100 in 40 CBMTG 0801 patients . Analysis focused on previously identified cGVHD cellular biomarkers including naive helper T cells recent thymic emigrant Th cells CD21 | Chronic graft versus host disease cGVHD marker utilization in clinical trials can elucidate the mechanisms of action. Anti thymocyte globulin ATG suppresses naive Th cell populations and expansion of CD56. natural killer cells. ATG primarily impacts on cGVHD through suppression of naive Th cells. |
S1083879119307839 | Umbilical cord blood transplantation is a curative procedure for patients with hematologic malignancies and genetic disorders and expands access to transplantation for non Caucasian patients unable to find a fully matched unrelated donor . In 2011 the US Food and Drug Administration required that unrelated UCBT be performed using either licensed UCB or unlicensed UCB under the Investigational New Drug program . The National Marrow Donor Program manages an IND under which 2456 patients underwent single or double UCBT between October 2011 and December 2016 . The median patient age was 31 years and 50 of children and 36 of adults were non Caucasian . The median time to neutrophil engraftment ie absolute neutrophil count 500 mm | Unlicensed umbilical cord blood units can be safely and effectively used for hematopoietic cell transplantation HCT in adult and pediatric patients. Unlicensed umbilical cord blood expands access to racially ethnically diverse patients in need of HCT. Further studies are required to compared licensed and unlicensed umbilical cord blood HCT. |
S1083879119307852 | Allogeneic hematopoietic cell transplant may improve long term multiple myeloma control through the graft versus myeloma effect . The Blood and Marrow Transplant Clinical Trials Network 0102 trial was a biologic assignment trial comparing tandem autologous transplant versus autologous followed by reduced intensity allogeneic transplant in patients with newly diagnosed MM with standard risk or high risk n 85 | Long term follow up of auto auto versus auto allo in newly diagnosed multiple myeloma patients confirms significant and durable reduction in risk of relapse with the auto allo approach. Auto allo transplant is associated with better 6 year PFS for high risk patients. Patients who relapsed after auto allo had longer postrelapse survival than patients who relapsed after auto auto transplant. |
S1083879119307864 | Polyphenols are a group of chemical substances found in plants with immunomodulatory antiproliferative and anti inflammatory properties that might be useful in the prophylaxis and treatment of graft versus host disease . Polyphenolic extract obtained from extra virgin olive oil decreased the activation and proliferation of activated T cells . In addition a decreased production of proinflammatory cytokines was observed upon exposure to PE . Western blot assays showed a marked inhibition of Akt phosphorylation and nuclear translocation of NF B in activated T cells . In a murine model of acute GVHD we observed that mice that received a diet supplemented in PE presented a higher survival rate and lower risk of developing GVHD when compared with the group that received a control diet . Histopathologic examination showed a significantly lower gut involvement in mice receiving PE with a decrease in proinflammatory cytokines in serum and the reestablishment of butyrate concentration in the gut . In conclusion PE obtained from EVOO exerted a potent immunomodulatory effect reducing the activation and proliferation of activated T cells and the production of proinflammatory cytokines . In a murine model of acute GVHD a PE supplemented diet reduced the incidence and severity of the disease and increased survival after transplantation . | Polyphenolic extract PE decreased activation IL 2 and TNF secretion and AKT P and NF B in T cells. A PE supplemented diet decreased acute graft versus host disease risk and improved survival in a mice model. A decrease in IL 2 IL 17 and TNF secretion was observed among mice receiving PE. Feces butyrate concentration was higher in mice receiving PE after transplantation. |
S1083879119307876 | Chronic graft versus host disease adversely affects patient quality of life functional status and survival after allogenic hematopoietic cell transplantation . The Lee Symptom Scale is a 30 item scale developed to measure the symptoms of cGVHD . Although the original 30 item scale uses a 1 month recall period we tested the reliability and validity of a 28 item scale with a 7 day recall period a format that is more appropriate for use in clinical trials . Results show the modified 7 day scale is reliable and valid in the modern era and may be used to assess the symptom burden of cGVHD in clinical trials . Using the distribution method a 5 to 6 point difference is considered clinically meaningful . | The 28 item modified Lee chronic GVHD symptom scale mLSS is valid and reliable. The scale takes 2 minutes to complete a 5 to 6 point difference is clinically meaningful. |
S1083879119307888 | After autologous hematopoietic cell transplantation in the first complete remission patients with acute myeloid leukemia may relapse and undergo allogeneic HCT in the second complete remission . The aim of this study was to analyze the outcome of allogeneic HCT performed in CR2 comparing patients with prior consolidation by autologous HCT versus patients with chemotherapy consolidation . Included were 2619 adults with allogeneic HCT in CR2 from 2000 to 2017 with or without prior autologous HCT . Patient groups were not entirely comparable patients with prior autologous HCT were younger had less often a favorable cytogenetic profile had more commonly donors other than matched siblings and more often received reduced intensity conditioning . In multivariate analysis nonrelapse mortality risks in patients with prior autologous HCT were 1.34 1.07 to 1.67 | Nonrelapse mortality after prior autologous hematopoietic cell transplantation HCT for subsequent allogeneic HCT in the second complete remission. Conditioning toxicity. Consolidation of acute myeloid leukemia in complete remission 1 by autologous HCT |
S1083879119308158 | Most children who may benefit from stem cell transplantation lack a matched related donor . Alternative donor transplantations with an unrelated donor or a partially matched related donor carry an increased risk of graft versus host disease and mortality compared with matched related donor transplantations . We hypothesized that a strategy of partial CD3 | The study cohort comprised children with leukemia who underwent partially CD3. depleted peripheral stem cell transplantation PSCT . Three year overall survival was 61.8 95 confidence interval CI 50.2 to 71.4 and event free survival was 52.0 95 CI 40.3 to 62.4 . Age 15 years and second complete remission were associated with worse outcomes. The incidence of severe chronic graft versus host disease was lower in CD3. than in T cell replete PSCT. |
S108387911930816X | Allogeneic hematopoietic cell transplantation is a demanding treatment with well established medical and psychosocial sequelae . Impacts on significant others are tremendous . Using an unfiltered qualitative approach we asked spouses of HCT recipients to talk about their thoughts and feelings regarding the transplantation and their role as caregiver . Recordings were transcribed and independently coded to identify recurrent patterns . Caregivers mentioned both negative and positive psychological impacts of HCT but the number of negative impacts was greater 164 versus 34 instances . The most frequently mentioned negative psychological impacts were anxiety worry fear feeling overloaded overwhelmed and uncertainty . Other emergent categories were roles responsibilities such as parenting work and treatment related tasks and coping strategies . The latter included both adaptive and maladaptive strategies . Despite the preponderance of negatively toned thoughts and feelings signs of adjustment emerged with mentions of positive psychological states such as optimism and gratitude and adaptive coping strategies such as active coping use of emotional support and self care . Interventions intended to facilitate adaptation to the HCT experience should involve strategies to help caregivers manage symptoms of distress and promote adaptive coping . | Caregivers mentioned a preponderance of negative psychological impacts. The most common negative psychological impacts were anxiety fear feeling overloaded overwhelmed and uncertainty. Despite these impacts a picture of resilience emerged with caregivers mentioning coping in adaptive ways such as using of emotional support. |
S1083879119308316 | Corneal clouding causing visual impairment is seen in nearly all patients with mucopolysaccharidosis type 1 . Hematopoietic cell transplantation is able to stabilize disease in many organs . Residual disease in several tissues is being increasingly recognized however . Data on the effect of HCT on ocular disease in patients with MPS 1 are contradictory . With this study we aim to clarify the long term effects of HCT on ocular disease in these patients . Best corrected visual acuity refraction intraocular pressure and slit lamp biomicroscopic and fundoscopic examinations including corneal clouding were collected prospectively from 24 patients with MPS 1 who underwent HCT successfully between 2003 and 2018 . The course of corneal clouding and BCVA after HCT were analyzed using a linear mixed model . Other parameters studied were clinical phenotype age at time of transplantation and hematologic enzyme activity after transplantation . Outcomes of additional ophthalmologic tests were described . In addition IDUA and galactosidase A enzyme activity and glycosaminoglycan concentration in tear fluid were determined . Corneal clouding stabilized in the first years after HCT but increased rapidly beyond 3 years | After initial stabilization corneal clouding is progressing in patients with mucopolysaccharidosis type 1 MPS 1 after treatment with hematopoietic cell transplantation HCT . Best corrected visual acuity is also worsening in MPS 1 patients after treatment with HCT. Despite normalized hematologic L iduronidase IDUA activity IDUA activity in tear fluid is still very low. Long term follow up and counseling of parents and patients undergoing HCT for MPS 1 is necessary. |
S1083879119308328 | Sinusoidal obstruction syndrome is a well recognized and potentially life threatening complication of hematopoietic stem cell transplantation . SOS arises from endothelial cell damage and hepatocellular injury mostly due to the transplantation conditioning regimens but also to other patient disease and treatment related factors . Understanding risk factors associated with the development of SOS is critical for early initiation of treatment or prophylaxis . The knowledge about genetic contribution is limited few studies investigated so far selected a set of genes . To get more comprehensive insight in the genetic component we performed an exome wide association study using genetic variants derived from whole exome sequencing . The analyses were performed in a discovery cohort composed of 87 pediatric patients undergoing HSCT following a busulfan containing conditioning regimen . Eight lead single nucleotide polymorphisms were identified after correction for multiple testing and subsequently analyzed in a validation cohort . Three SNPs were successfully replicated including rs17146905 | Sinusoidal obstruction syndrome SOS is a complication of hematopoietic stem cell transplantation. Whole exome sequencing was performed to identify the genetic contribution to SOS. Exome wide association study identified 8 lead signals in the discovery cohort. Three loci. and. were validated in the replication group. The finding can be useful for designing personalized prophylactic strategies. |
S108387911930833X | Chimeric antigen receptor T cell therapy a new immunotherapy for relapsed and refractory hematologic malignancies can be accompanied by adverse events including coagulation disorders . Here we performed a comprehensive analysis of coagulation parameters in 100 patients with R R hematologic malignancies after receiving CAR T cell therapy to illuminate the profiles of coagulation disorders and to facilitate the management of coagulation disorders . A high incidence of coagulation disorders was observed including elevated D dimer increased fibrinogen degradation product decreased fibrinogen prolonged activated partial thromboplastin time and prolonged prothrombin time . Coagulation disorders occurred mainly during day 6 to day 20 after CAR T cell infusion . The changes in coagulation parameters were associated with high tumor burden in acute lymphoblastic leukemia more lines of prior therapies lower baseline platelet count and especially cytokine release syndrome . Disseminated intravascular coagulation was found in 7 patients with grade 3 CRS and indicated a poor prognosis . Our study suggests that coagulation disorders are manageable in most patients after CAR T cell therapy . Coexistence of DIC and severe CRS is closely related to nonrelapsed deaths during the acute toxicity phase and effective and timely treatment is the key to reduce nonrelapse mortality for patients with DIC and severe CRS . | A high incidence of coagulation disorders was observed after chimeric antigen receptor CAR T cell therapy infusion. The changes of coagulation parameters were associated with cytokine release syndrome CRS . Disseminated intravascular coagulation was found in patients with severe CRS and indicated a poor prognosis. Coagulation disorders are manageable in most patients after CAR T cell infusion. |
S1083879119308341 | In this retrospective analysis we evaluated the impact of age on the outcome of patients with multiple myeloma who received an autologous hematopoietic stem cell transplantation at our institution . A total of 1128 patients were divided into the older and the younger groups . Compared with the younger cohort older patients had a higher International Staging System stage versus 215 ISS III 52 versus 211 | This retrospective analysis compares the outcome of patients with newly diagnosed multiple myeloma NDMM aged 70 versus 70 years n 1128 . Age cutoff at 70 years is higher than in most other retrospective studies that performed a similar analysis. There is an association between age at transplantation with progression free survival and overall survival of patients with NDMM who underwent autologous hematopoietic stem cell transplantation. |
S1083879119308353 | Hematopoietic stem cell transplantation is the only curative treatment for juvenile myelomonocytic leukemia but few large studies of HSCT for JMML exist . Using data from the Japan Society for Hematopoietic Cell Transplantation registry we analyzed the outcomes of 129 children with JMML who underwent HSCT between 2000 and 2011 . The 5 year overall survival rate and cumulative incidence of relapse were 64 and 34 respectively . A regimen of busulfan fludarabine melphalan was the most commonly used and provided the best outcomes the 5 year OS rate reached 73 and the cumulative incidences of relapse and transplantation related mortality were 26 and 9 respectively . In contrast the use of the irradiation based myeloablative regimen was the most significant risk factor for OS 2.92 | Hematopoietic cell transplantation is the only curative therapy for juvenile myelomonocytic leukemia. Busulfan fludarabine melphalan seems to offer the best chance of long term survival. Chronic graft versus host disease correlates with improved survival by reducing relapse. Treatment strategies enhancing graft versus leukemia effects may further improve outcome. |
S1083879119308377 | Bronchiolitis obliterans syndrome after allogeneic hematopoietic cell transplantation is often diagnosed at a late stage when lung dysfunction is severe and irreversible . Identifying patients early after transplantation may offer improved strategies for early detection that could avert the morbidity and mortality of BOS . This study aimed to determine whether a decline in lung function before and early after allo HCT are associated with a risk of BOS beyond 6 months post transplantation . In a single center cohort of 2941 allo HCT recipients 186 met National Institutes of Health criteria for BOS . Pretransplantation and post transplantation day 80 spirometric parameters were analyzed as continuous variables and included in a multivariable model with other factors including donor source graft source conditioning regimen use of total body irradiation and immunoglobulin levels . Pre transplantation forced expiratory flow between 25 and 75 of maximum FEF | Identifying patients at risk for bronchiolitis obliterans syndrome BOS after allogeneic hematopoietic cell transplantation may offer improved strategies for early detection. Declines in pretransplantation and early post transplantation spirometric parameters are associated with risk of developing BOS. A reduction in FEF. at day 80 may be more important than FEV. in predicting BOS development. |
S1083879119308389 | Prolonged thrombocytopenia after hematopoietic stem cell transplantation is a strong risk factor for transplantation related morbidity and mortality and no standard treatment guideline exists . Thrombopoietin receptor agonists eltrombopag and romiplostim increases the platelet production and are being increasingly used in various conditions with thrombocytopenia . In this review we present an overview of these TPO RAs and review their efficacy and safety in prolonged post HSCT thrombocytopenia . Through a systematic literature search we identified 25 reports describing their use for this indication . Thirteen reports described the use of eltrombopag in 78 patients with prolonged isolated thrombocytopenia and 43 patients with secondary failure of platelet recovery . A consistent and durable response with a rise in platelet counts 5010 | Prolonged thrombocytopenia after hematopoietic stem cell transplantation HSCT is a strong risk factor for transplantation related morbidity and mortality. No common consensus exists for the uniform classification and management of prolonged thrombocytopenia after HSCT. The available literature inconsistently describes post HSCT thrombocytopenia as either prolonged isolated thrombocytopenia PIT or secondary failure of platelet recovery SFPR . Thrombopoietin receptor agonists eltrombopag and romiplostim are being increasingly to treat patients with prolonged post HSCT thrombocytopenia. Our extensive literature review suggests that patients with prolonged post HSCT thrombocytopenia may respond to both eltrombopag overall response rate ORR 70 and romiplostim ORR 82 with no evidence of serious adverse effects. However the overall strength of evidence is weak in view of retrospective nature of the studies lack of control groups heterogeneity of data and potential for publication bias. |
S1083879119308390 | Allogeneic hematopoietic stem cell transplantation is the only available curative treatment option for patients with aggressive adult T cell leukemia lymphoma . Donor human T cell leukemia virus 1 seropositivity is a critical concern when choosing relative donors as they are not usually recommended due solely to the occurrence of donor derived ATL . A previous report suggested that allo HCT with an HTLV 1 seropositive donor increased ATL related mortality . We updated the risk assessment for choosing an HTLV 1 seropositive allo HCT donor for ATL . Our current registry data which include larger numbers of HTLV 1 seropositive donors and longer observation periods revealed no significant difference in overall survival 0.93 95 confidence interval 0.70 1.24 | We assessed the effect of donor human T cell leukemia virus 1 serostatus on outcomes of allogeneic hematopoietic stem cell transplantation allo HCT in adult T cell leukemia lymphoma. There was no significant difference in overall survival or incidence of mortality. This might aid the choice of appropriate and timely alternative donors for allo HCT. |
S1083879119308675 | Congenital erythropoietic porphyria is a rare disease characterized by erosive photosensitivity and chronic hemolysis due to a defect of the enzyme uroporphyrinogen III synthase . To date hematopoietic stem cell transplantation is the only curative therapy for the devastating early and severe form of the disease . We describe 6 patients with CEP treated with HSCT between 1994 and 2016 in our center including 2 of the very first living patients treated more than 20 years ago . Four patients are doing well at 6 to 25 years post HSCT with near normal biochemical parameters of porphyrin metabolism without the cutaneous or hematologic features of CEP . One patient died within the first year after HSCT from severe graft versus host disease and 1 child died of unexplained acute hepatic failure at 1 year after HSCT despite full donor chimerism . Retrospectively it appears that all but 1 child had increased transaminase activity with onset from the early postnatal period which was significantly more marked in the child who died of liver failure . In contrast liver function values progressively normalized after engraftment in all other children . Liver pathology before HSCT for 3 patients revealed varying degrees of portal centrilobular and perisinusoidal fibrosis clarification of hepatocytes and cytosolic porphyrin deposits . The liver porphyrin content in biopsy specimens was 60 times the normal values . Despite difficult engraftment the long term efficacy of HSCT in CEP appears to be favorable and reinforces its benefits for the severe form of CEP . Hepatic involvement requires careful evaluation before and after HSCT and further investigation into its pathophysiology and care . | The very first still living recipients of hematopoietic stem cell transplantation HSCT for early and severe forms of congenital erythropoietic porphyria CEP 25 and 22 years ago are healthy and asymptomatic with sustained corrected uroporphyrinogen III synthase activity. Intrinsic hepatic involvement of varying intensity is present at birth with either a favorable or a fatal outcome despite HSCT engraftment. Liver pathology revealed varying degrees of portal centrilobular and perisinusoidal fibrosis clarification of hepatocytes and cytosolic porphyrin deposits. Due to the risks and difficulties of HSCT the indication remains limited to the severe form of CEP. |
S1083879119316507 | Acute pancreatitis has been recognized as an uncommon yet potentially lethal complication after hematopoietic stem cell transplant . This retrospective nested case control study reviewed data from 5284 consecutive patients who underwent allogeneic HSCT between 2009 and 2018 at a single center identifying 40 patients with AP after allo HSCT . The diagnosis and severity of AP were established and classified according to existing criteria . Younger age | We report the incidence of acute pancreatitis AP after allo HSCT. We identify younger age grades II to IV aGVHD a history of DLI and pre existing gallstones as independent risk factors of post transplant AP. We describe the outcomes of patients with post transplant AP. We establish an exploratory risk score model to help risk stratification in such patients. |
S1083879119316519 | Antibiotic induced gut dysbiosis has been associated with poor outcomes after intensive therapy . We evaluated the effect of levofloxacin the most commonly used prophylactic antibacterial antibiotic during intensive chemotherapy and allogeneic hematopoietic cell transplantation on the gut microbiota in 2 cohorts of patients 1 cohort comprising 20 patients with acute leukemia receiving intensive chemotherapy and the other cohort comprising 20 allo HCT recipients . 16S rRNA gene sequencing of thrice weekly collected stool samples permitted a comparison between intervals with no antibacterial antibiotic exposure and those with only LEVO exposure . In mixed effects modeling the only variables influenced by LEVO were the relative abundances of | Prophylactic levofloxacin LEVO during intensive therapy did not reduce gut microbiota diversity. LEVO exposure was associated with a relative reduction of. LEVO exposure was associated with a relative expansion of |
S1083879119316520 | Patients with acute myelogenous leukemia who undergo killer immunoglobulin like receptor mismatched haploidentical hematopoietic stem cell transplantation have improved survival . Children s Oncology Group AAML05P1 is a prospective phase 2 trial of unrelated donor HSCT in which KIR typing of donors was available to the treating physician at donor selection aiming to determine feasibility of prospective selection of KIR mismatched donors and effect on outcomes . Patients age 30 years with high risk AML at presentation or relapsed AML were eligible the study accrued 90 evaluable patients . After enrollment as many as 5 potential URD samples were KIR typed in a central laboratory and results reported to the treating physician who made the final donor selection . Cases were categorized as KIR matched or KIR mismatched using different published strategies . Overall survival disease free survival and relapse did not differ significantly by KIR mismatch status . Acute graft versus host disease was significantly lower in recipients of KIR mismatched stem cells 35 versus 60 | KIR mismatching did not improve disease free survival in children transplanted with unrelated donor stem cells for AML using in vivo T cell depletion with ATG. KIR mismatching did alter the kinetics of NK cell receptor acquisition on donor cells after stem cell transplantation in children. |
S1083879119316532 | Common respiratory viral infections frequently complicate hematopoietic stem cell transplantation . We conducted a retrospective single center observational cohort study to determine the incidence of CRVI in patients who received an allogeneic or autologous HSCT at the Royal Adelaide Hospital between 2009 and 2017 . The median follow up was 8.9 and 4.5 years for auto and allo HSCT recipients respectively . There were 149 CRVI episodes in 74 patients with rhinovirus being the most commonly isolated virus . The majority of CRVIs occurred more than 100 days post HSCT and 67 were diagnosed in the outpatient setting . There was evidence of lower respiratory tract infection in 45.6 of CRVIs . On multivariate logistic regression analysis coviral infections and cytomegalovirus viremia were independent risk factors for progression of CRVI to LRTI . Ten CRVI episodes resulted in admission to intensive care for ventilatory support and 8 patients died within 30 days of CRVI diagnosis . In our study 10.4 of HSCT recipients experienced a CRVI post transplant primarily causing late morbidity and potentially mortality . Prevention with strict infection control practices vaccination and patient education is essential . | Of HSCT recipients 10.4 experienced common respiratory viral infections CRVIs . Rhinovirus infection was common accounting for nearly 50 of CRVIs. Of CRVIs 45.6 were complicated by lower respiratory tract infection LRTI . Respiratory viral coinfection and cytomegalovirus viremia were risk factors for LRTI. Of CRVI episodes 6.7 resulted in intensive care admission. |
S1083879119316544 | This is a multicenter retrospective comparison of 2 myeloablative conditioning regimens in 454 patients with acute myeloid leukemia in remission busulfan and fludarabine versus thiotepa busulfan and fludarabine . Eligible for this study were patients allografted between January 2008 and December 2018 in 10 transplant centers with AML in first or second remission 201 patients received BUFLU whereas 253 received TBF . The 2 groups were comparable for age | The combination of thiotepa and busulfan fludarabine reduces the risk of relapse in patients with remission acute myeloid leukemia compared with myeloablative busulfan fludarabine. The effect is independent of donor type and graft versus host disease prophylaxis. |
S1083879119317318 | Gemtuzumab ozogamicin therapy before allogeneic hematopoietic cell transplantation has been historically associated with an increased risk of hepatic veno occlusive disease sinusoidal obstruction syndrome in patients with acute myeloid leukemia . The current analysis examined VOD SOS risk and outcomes in a cohort of patients who in recent years were reported to the Center for International Blood and Marrow Transplant Research . Adults with AML who had GO exposure before myeloablative alloHCT were matched 1 4 by age and disease status at transplant to recipients without GO exposure . One hundred thirty seven patients with GO exposure and 548 matched control subjects who underwent alloHCT between 2008 and 2011 were included in this analysis . With a median 8 year follow up of survivors the 5 year overall survival probability was similar in the 2 cohorts 38 and 38 in the GO exposed versus control groups | VOD SOS incidence at 100 days post HCT was 4 versus 3 in GO exposed adults versus control subjects. Five year overall survival probability was 38 in both groups. GO exposure before HCT was not associated with an increased risk of VOD SOS or death. |
S108387911931732X | Immunosuppressive drugs are an inherent component of hematopoietic stem cell transplantation for the prevention of acute graft versus host disease . Circulating 1 antitrypsin a serine protease inhibitor produced predominantly by hepatocytes that rises during acute phase responses is lost in patient s stool due to gastrointestinal GVHD and its augmentation has been found to attenuate GVHD . Here we explored the effect of immunosuppressive drugs on hepatocyte production of AAT and intestinal epithelial gap repair . The effect of commonly used immunosuppressants on AAT production was examined in vitro using HepG2 cells and primary mouse hepatocytes and their impact on human intestinal epithelial cell line gap repair was evaluated . Sera from 12 allogeneic HSCT recipients obtained at 14 days post transplantation predating the diagnosis of GVHD were examined for reepithelialization with added clinical grade AAT . Rapamycin compromised AAT production under inflammatory conditions . Mycophenolate mofetil and cyclosporine A inhibited reepithelialization AAT minimized the effect of CSA . Patient sera displayed superior gap repair with exogenous AAT . Functional insufficiency in circulating AAT may be the result of drug toxicities leading to ineffective gut reepithelization and compromised gut lining . Taken together our data strengthen the rationale for incorporating AAT augmentation therapy into immunosuppressive treatment protocols . | Rapamycin decreases 1 antitrypsin production by hepatocytes under inflammation. Mycophenolate mofetil inhibits wound repair in intestinal epithelial cell line. Exogenous 1 antitrypsin enhances allo HSCT recipients sera wound repair capability. |
S1083879119317331 | HLA haploidentical allogeneic hematopoietic cell transplantation using post transplantation cyclophosphamide is becoming the standard of care for patients without an HLA matched related or unrelated donor . PT Cy haplo can give more patients the opportunity to undergo allo HCT because most patients have multiple available HLA haploidentical related donor candidates . The optimal donor selection algorithm in the PT Cy haplo setting has not yet been established however . To contribute to the establishment of a donor selection formula based on disease status and killer cell immunoglobulin like receptor genotype we retrospectively analyzed 91 patients who underwent PT Cy haplo at our institution . In both patients and donors HLA allele genotyping was performed for HLA A B C and DRB1 and 16 KIR genes were genotyped . Patients in complete remission who underwent PT Cy haplo from a | Donor. was associated with reduced risk of relapse after HLA haploidentical allogeneic hematopoietic cell transplantation allo HCT using post transplantation cyclophosphamide PT Cy haplo . Donor. was associated with improved overall survival with PT Cy haplo. GVL effect via NK cell alloreactivity was exerted in CR but not in non CR. Donor. genotyping and disease status should be assessed for donor selection. Elucidating mechanisms involved could lead to novel strategies for relapse therapy. |
S1083879119317343 | Reduced intensity conditioning regimens improved HLA matching and better supportive care allow allogeneic stem cell transplant to be offered to older patients . Only a small percentage of eligible patients between ages 65 and 74 years actually undergo alloSCT and comprehensive outcome data from the aging population are still lacking . We examined the outcome of older patients who underwent alloSCT using melphalan based RIC for hematologic malignancies at our institution . We identified 125 patients older than 65 years who underwent matched related donor matched unrelated donor or combined haploidentical umbilical cord alloSCT between 2012 through November 2017 . Among them 52 and 70 had respectively intermediate and high very high Center for International Blood and Marrow Transplant Research disease risk index . One hundred six patients received fludarabine melphalan based RIC regimen with either antithymocyte globulin or alemtuzumab . | Older patients with hematologic malignancies tolerate melphalan based RIC alloSCT with acceptable survival outcomes. Using. T cell depletion the incidence of cGVHD is very low and quality of life of survivors is excellent. Outcomes of related unrelated and haplo cord alloSCT are comparable. |
S1083879119317380 | Although cord blood transplantation extends allograft access patient comorbidities chemoradiation and nephrotoxic medications all contribute to acute kidney injury risk . We analyzed AKI in adult myeloablative CBT recipients who underwent transplantation from 2006 to 2017 for hematologic malignancies using cyclosporine A mycophenolate mofetil immunosuppression . Maximum grades of AKI were calculated using Kidney Disease Improving Global Outcomes definitions . In total 153 patients 114 153 acute leukemia 27 153 African 88 153 cytomegalovirus seropositive median age adjusted hematopoietic cell comorbidity index 3 median pretransplant albumin 4.0 g dL underwent transplantation . The day 100 cumulative incidence of grade 1 3 AKI was 83 77 89 and grade 2 3 AKI incidence was 54 . Mean CSA level preceding AKI onset was high . In multivariate analysis African ancestry addition of haploidentical CD34 | Day 100 grade 2 to 3 acute kidney injury AKI incidence is high after adult cord blood transplantation. Grade 1 to 2 AKI can be present with a normal creatinine. A higher pretransplant serum albumin protects against AKI. Critical illness and nephrotoxic drugs increase AKI risk. Early post transplant AKI increases 2 year chronic kidney disease risk. |
S108387912030001X | Extracorporeal photopheresis is an established treatment strategy in steroid refractory graft versus host disease . This study s main objective was to analyze the clinical response and impact of ECP therapy in steroid dose reduction . A retrospective observational series of 113 patients from 7 transplantation centers was analyzed . Sixty five patients had acute GVHD and 48 had chronic GVHD . All ECP procedures were performed with the off line system . The median number of procedures until achievement of initial response was 3 for both patients with aGVHD and those with cGVHD . ECP was the second line therapy in 48 of the aGVHD cases and in 50 of the cGVHD cases . 71 of the cases of aGVHD were grade III IV and 69 of the cases of cGVHD were severe . The overall response rate on day 28 was 53 rate 45 in the patients with aGVHD and 67 in those with cGVHD . Skin was the most frequently involved organ with a response rate of 58 in the patients with aGVHD and 69 in those with cGVHD . At the end of ECP treatment 60 of patients treated for aGVHD who responded were able to stop steroid therapy with a median dose reduction of 100 . Significant differences in overall survival were observed for patients responding to ECP with aGVHD 4.3 | Photopheresis is an effective treatment for refractory graft versus host disease GVHD . Overall response to treatment is the most important variable for survival. Gastrointestinal GVHD carries a worse prognosis and response. Steroid dose reduction is associated with improved survival in chronic GVHD. |
S1083879120300021 | The newly developed 6 hydroxychromanol derivate SUL 109 was shown to provide protection during hypothermic storage of several cell lines but has not been evaluated in hematopoietic stem cells . Hypothermic preservation of HSCs would be preferred over short term cryopreservation to prevent cell loss during freezing thawing and would be particularly useful for short term storage such as during conditioning of patients or transport of HSC transplants . Here we cultured human CD34 | SUL 109 a newly developed 6 chromanol derivate is an easy to use nontoxic cell culture additive that provides protection during hypothermic storage of hematopoietic stem cells HSCs . SUL 109 improves cell survival of immature CD34. CD38. cells during hypothermic storage and preserves the multilineage capacity of human CD34. UCB cells. SUL 109 effectively lowers reactive oxygen species during hypothermic storage and preserves the engraftment potential of HSCs after hypothermia. |
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